• Cell Biology - Department of Biology - Faculty of Science - Utrecht University
  • Cell Biology - Department of Biology - Faculty of Science - Utrecht University
  • Cell Biology - Department of Biology - Faculty of Science - Utrecht University
Cell Biology

Anna Akhmanova: Cellular Dynamics

CV - Research - Projects - Lab members - Publications

 


annaakhmanovaProf. Dr. Anna Akhmanova
Cell Biology
Faculty of Science, Utrecht University
Kruytgebouw, room O503
Padualaan 8, 3584 CH, Utrecht
The Netherlands
Tel. 31-(0)30-253 2328
Fax 31-(0)30-253 2837
e-mail: This email address is being protected from spambots. You need JavaScript enabled to view it.

 


 Curriculum Vitae

Anna Akhmanova studied biochemistry and molecular biology at the Moscow State University. She received her PhD in 1997 at the University of Nijmegen. She worked as a post-doc at the Department of Microbiology and Evolutionary Biology at the University of Nijmegen and at the Department of Cell Biology at the Erasmus Medical Center in Rotterdam. In 2001, she has started her own research group at the Department of Cell Biology at the Erasmus Medical Center. Since 2011, Anna Akhmanova is professor of Cell Biology at Utrecht University.

Anna Akhmanova is a recipient of the ALW Vernieuwingsimpuls VIDI (2001) and VICI awards (2007), and an ERC Synergy grant (2013). She is the Chair of the board of the Netherlands Microscopy Society and a member of the European Molecular Biology Organization (EMBO).

A pdf of a short CV can be downloaded here.

 


 Research summary

My group studies cytoskeletal organization and trafficking processes, which contribute to cell polarization, differentiation, vertebrate development and human disease. We are interested in understanding, at a systems level, in how different aspects of cell architecture are coordinated.

The main focus of our studies is the microtubule cytoskeleton. Our research relies on combining high-resolution live cell imaging and quantitative analysis of cytoskeletal dynamics, measurement of protein dynamics using advanced microscopic assays, in vitro reconstitution of dynamic cytoskeleton-based processes and different methods of identification of protein-protein interactions (in vitro binding studies, pull-down assays, yeast two-hybrid screens and mass spectrometry-based protein identification). In addition to cultured cells, we employ mouse knockout technologies and couple mouse genetic modification (such as GFP knock-in technology) to live tissue imaging. In collaboration with mathematicians we are working on development of automated analysis and modeling of cytoskeletal dynamics and vesicle transport.

One of the main topics of our research is the structure and function of microtubule plus-end tracking proteins - a group of factors that associate specifically with the growing microtubule ends, regulate microtubule dynamics and their interactions with various cellular structures, such as the actin cytoskeleton, focal adhesions and cell-cell contacts.

In another line of study, we investigate molecular mechanisms of microtubule-based vesicle transport. We identified several linkers between vesicles and microtubule motors and developed novel assays to demonstrate specific functions of these linkers in recruitment of motor proteins to membrane organelles. As a model system, we are currently investigating the process of constitutive exocytosis, which received relatively little attention in the literature in spite of its fundamental importance.

Microtubule-based processes are essential for cell division, normal functioning of large cells such as neurons and for intracellular transport of pathogens; therefore, our studies are relevant for combating abnormal cell proliferation, neurodegeneration and infectious diseases.

 


 Projects

Microtubule Plus End Tracking Proteins (+TIPs)
Mechanisms of bi-directional microtubule-based transport
Mechanisms of exocytotic vesicle fusion with the plasma membrane

 

 Microtubule Plus End Tracking Proteins (+TIPs)

Microtubules play an essential role in mitosis, positioning and movement of cellular organelles, maintenance of cell shape and cell motility. Microtubules are highly dynamic: they continuously switch between phases of growth and shrinkage. This phenomenon, termed dynamic instability, is essential for formation and remodeling of microtubule networks.

Microtubules are hollow cylindrical polymers, which are intrinsically polarized. Microtubule plus-ends are the fast-growing ends in vitro and the only ends that grow in cells. The opposite (minus) ends can slowly grow in vitro, while in cells they are usually stabilized or serve as the sites of disassembly. A number of specialized proteins and protein complexes that are conserved in all eukaryotes specifically accumulate at growing microtubule plus ends, and are collectively referred to as plus-end-tracking proteins (+TIP). We are interested in understanding how +TIPs interact with microtubule ends and with each other, and how they regulate microtubule dynamics and microtubule interactions with different cellular structures.

+TIPs include motors, adaptors and linker proteins from different structurally unrelated families. They all share the capacity to form comet-like accumulations at the growing microtubule tips.

picture1

A portion of a COS-1 cell, fixed and stained for CLIP-170 (green), and microtubules (red). Note the comet-like appearance of CLIP-170 staining at the microtubule plus ends.

 

 

 

 

picture2corrected

Many +TIPs do not recognize the plus ends directly but rather bind to them through the highly conserved members of the EB (End Binding) protein family.

 

 

 

 

 

 

 

Some +TIPs specifically localize to certain cellular structures, such as mitotic kinetochores or the cell cortex, and regulate microtubule dynamics in the vicinity of these structures. For example, CLASPs stabilize microtubules at the leading edge of migrating fibroblasts.

picture3

Localization of CLASP2 (green) to the leading edge of a migrating mouse 3T3 fibroblast. Stable (acetylated) microtubules are shown in red.

 

 

 

 

 

Our studies are aimed at revealing the functions of +TIPs and the molecular mechanisms underlying their activities. They heavily rely on advanced microscopy techniques such as wide field, confocal and Total Internal Reflection Fluorescence Microscopy with high spatial and temporal resolution.

Current projects:

  • Identification of the complete set of mammalian +TIPs
  • Regulation of microtubule dynamics at the cell cortex
  • Functional cross-talk between dynamic microtubules and cell-cell and cell-matrix adhesions
  • Effects of microtubule-active drugs on +TIP interactions with microtubules
  • Characterization of +TIP dynamics in vitro using single molecule approaches
  • Reconstitution of +TIP-mediated regulation of microtubule dynamics in vitro using purified proteins
  • Development of mouse models to study +TIP function and image +TIP dynamics

 

 Mechanisms of bi-directional microtubule-based transport

Various cellular organelles (mitochondria, peroxisomes, lysosomes, endosomes, ER- and Golgi-derived vesicles) are transported within cells along cytoskeletal tracks. Long-range intracellular transport occurs along microtubules and depends on kinesin and dynein motors. Cytoplasmic dynein (as opposed to flagellar dyneins, which are responsible for the movements of the cilia and flagella) is a microtubule minus end-directed motor, which is involved in the transport of membrane organelles, mRNAs and protein complexes. The aim of our research is to understand how dynein is linked to various cargos and how dynein activity is coordinated with that of plus end-directed motors, kinesins, present on the same cargos. We also investigate how different signaling pathways regulate motor activities.

Our current studies are focused on the evolutionary conserved adaptor protein Bicaudal D, which can interact with dynein-dynactin complex and also with kinesin-1. In flies, Bicaudal D plays an important role in dynein-dependent polarized transport of mRNAs. In mammalian cells, Bicaudal D homologues are involved in dynein-dependent transport of exocytotic vesicles positive for the small GTPase Rab6, as well as in dynein and kinesin-mediated positioning of the nucleus and the centrosome at the onset of mitosis.

picture4

Bicaudal D1 (green) and Rab6 (red) colocalise at the Golgi complex and cytoplasmic vesicles in interphase HeLa cells.

 

 

 

 

 

picture5

Dual color time lapse live imaging of a Rab6-postive exocytotic vesicle (green) moving on a microtubule (red). Note that the vesicle changes the direction of movement: it switches from plus end directed to minus end directed transport.

 

We use multicolor microscopy techniques such as wide field, confocal and Total Internal Reflection Fluorescence Microscopy with high spatial and temporal resolution to study vesicle movement along microtubules and different biochemical techniques to investigate the interactions of Bicaudal D2 with motors and cargo molecules.

Current projects:

  • Identification of the full set of kinesin motors involved in transport of Rab6-bound exocytotic vesicles
  • Identification of molecular basis of the interaction of Bicaudal D with dynein and dynactin
  • Characterization of the signaling pathways regulating Bicaudal D association with motors and cargos

 

 Mechanisms of exocytotic vesicle fusion with the plasma membrane

Exocytotic carriers exit from the Golgi apparatus, move along microtubule tracks towards cell periphery and then fuse with the plasma membrane. Recently, we found that the same cortical complexes are involved in attachment of microtubule plus ends to the plasma membrane and in promoting vesicle fusion. These complexes contain the lipid binding protein LL5β and the adaptor protein ELKS (also known as ERC1 or Rab6IP2). These complexes depend on integrins for their localization at the plasma membrane and are intimately associated with focal adhesions.

Our aim is to understand how these complexes are assembled and regulated, how they control microtubule attachment and dynamics, and what is the molecular mechanism underlying the ability to enhance vesicle fusion. Since ELKS protein was also found as an important part of the NF-κB signaling pathway, we are also interested in the functional interactions between the components of this pathway, microtubule stabilization and vesicle fusion machinery.

picture6

Cortical patches positive for LL5β (red) serve as microtubule attachment sites in a HeLa cell (microtubules are shown in green).

 

 

 

 

newpicture7Cortical patches positive for LL5β (green) accumulate around focal adhesions visualized by staining for focal adhesion kinase (red). This phenomenon is particularly apparent when microtubules are disassembled with microtubule-depolymerizing drug nocodazole.

 

 

Current projects:

  • Identification of structural components of the LL5β-ELKS protein complexes
  • Characterization of microtubule-stabilizing and destabilizing activities associated with LL5β-ELKS complexes
  • Identification of molecular links between LL5β-ELKS complexes and SNAREs involved in exocytotic vesicle fusion
  • Functional cross-talk between NF-κB signaling, microtubule stabilization and vesicle fusion
  • Localization LL5β-ELKS complexes in mouse tissues
  • Function of LL5β-ELKS complexes in pancreatic β-cells and insulin secretion

 


 Lab members

Research assistant:  
Ilya Grigoriev This email address is being protected from spambots. You need JavaScript enabled to view it.
   
Technician:  
Bart de Haan This email address is being protected from spambots. You need JavaScript enabled to view it.
   
Postdocs:  
Kai Jiang This email address is being protected from spambots. You need JavaScript enabled to view it.
Benjamin Bouchet This email address is being protected from spambots. You need JavaScript enabled to view it.
Harinath Doodhi This email address is being protected from spambots. You need JavaScript enabled to view it.
Ruddi Rodriquez Garcia This email address is being protected from spambots. You need JavaScript enabled to view it.
   
PhD students:  
Carol Yu This email address is being protected from spambots. You need JavaScript enabled to view it.
Andrea Marques This email address is being protected from spambots. You need JavaScript enabled to view it.
Helma van Riel This email address is being protected from spambots. You need JavaScript enabled to view it.
Jingchao Wu This email address is being protected from spambots. You need JavaScript enabled to view it.
Qingyang Liu This email address is being protected from spambots. You need JavaScript enabled to view it.
Ivar Noordstra This email address is being protected from spambots. You need JavaScript enabled to view it.
Amol Aher This email address is being protected from spambots. You need JavaScript enabled to view it.
Dieudonnée van de Willige This email address is being protected from spambots. You need JavaScript enabled to view it.
Ruben Schmidt This email address is being protected from spambots. You need JavaScript enabled to view it.

 


 Publications

Research Articles - Reviews

Research Articles

2013

Shahbazi MN, Megias D, Epifano C, Akhmanova A, Gundersen GG, Fuchs E, and Perez-Moreno M. CLASP2 interacts with p120-catenin and governs microtubule dynamics at adherens junctions. J Cell Biol. 2013 Dec 23, 203(6): 1043-61. PMID: 24368809.

van der Vaart B, van Riel WE, Doodhi H, Kevenaar JT, Katrukha EA, Gumy L, Bouchet BP, Grigoriev I, Spangler SA, Yu KL, Wulf PS, Wu J, Lansbergen G, van Battum EY, Pasterkamp RJ, Mimori-Kiyosue Y, Demmers J, Olieric N, Maly IV, Hoogenraad CC, and Akhmanova A. CFEOM1-associated kinesin KIF21A is a cortical microtubule growth inhibitor. Dev Cell. 2013 Oct 28, 27(2): 145-60. PMID: 24120883.

Hu DJ, Baffet AD, Nayak T, Akhmanova A, Doye V, and Vallee RB. Dynein recruitment to nuclear pores activates apical nuclear migration and mitotic entry in brain progenitor cells. Cell. 2013 Sep 12, 154(6): 1300-13. PMID: 24034252.

van Spronsen M, van Battum EY, Kuijpers M, Vangoor VR, Rietman ML, Pothof J, Gumy LF, van Ijcken WF, Akhmanova A, Pasterkamp RJ, and Hoogenraad CC. Developmental and activity-dependent miRNA expression profiling in primary hippocampal neuron cultures. PLoS One. 2013, 8(10): e74907. PMID: 24098357.

Sen I, Veprintsev D, Akhmanova A, and Steinmetz MO. End binding proteins are obligatory dimers. PLoS One. 2013, 8(9): e74448. PMID: 24040250.

Berends CW, Munoz J, Portegijs V, Schmidt R, Grigoriev I, Boxem M, Akhmanova A, Heck AJ, and van den Heuvel S. F-actin asymmetry and the endoplasmic reticulum-associated TCC-1 protein contribute to stereotypic spindle movements in the Caenorhabditis elegans embryo. Mol Biol Cell. 2013 Jul, 24(14): 2201-15. PMID: 23699393.

Kuijpers M, Yu KL, Teuling E, Akhmanova A, Jaarsma D, and Hoogenraad CC. The ALS8 protein VAPB interacts with the ER-Golgi recycling protein YIF1A and regulates membrane delivery into dendrites. EMBO J. 2013 Jul 17, 32(14): 2056-72. PMID: 23736259.

Bulgakova NA, Grigoriev I, Yap AS, Akhmanova A, and Brown NH. Dynamic microtubules produce an asymmetric E-cadherin-Bazooka complex to maintain segment boundaries. J Cell Biol. 2013 Jun 10, 201(6): 887-901. PMID: 23751496.

Ferreira JG, Pereira AJ, Akhmanova A, and Maiato H. Aurora B spatially regulates EB3 phosphorylation to coordinate daughter cell adhesion with cytokinesis. J Cell Biol. 2013 May 27, 201(5): 709-24. PMID: 23712260.

Kapitein LC, van Bergeijk P, Lipka J, Keijzer N, Wulf PS, Katrukha EA, Akhmanova A, and Hoogenraad CC. Myosin-V opposes microtubule-based cargo transport and drives directional motility on cortical actin. Curr Biol. 2013 May 6, 23(9): 828-34. PMID: 23602478.

Molina A, Velot L, Ghouinem L, Abdelkarim M, Bouchet BP, Luissint AC, Bouhlel I, Morel M, Sapharikas E, Di Tommaso A, Honore S, Braguer D, Gruel N, Vincent-Salomon A, Delattre O, Sigal-Zafrani B, Andre F, Terris B, Akhmanova A, Di Benedetto M, Nahmias C, and Rodrigues-Ferreira S. ATIP3, a novel prognostic marker of breast cancer patient survival, limits cancer cell migration and slows metastatic progression by regulating microtubule dynamics. Cancer Res. 2013 May 1, 73(9): 2905-15. PMID: 23396587.

Jeffery JM, Grigoriev I, Poser I, van der Horst A, Hamilton N, Waterhouse N, Bleier J, Subramaniam VN, Maly IV, Akhmanova A, and Khanna KK. Centrobin regulates centrosome function in interphase cells by limiting pericentriolar matrix recruitment. Cell Cycle. 2013 Mar 15, 12(6): 899-906. PMID: 23442802.

van Spronsen M, Mikhaylova M, Lipka J, Schlager MA, van den Heuvel DJ, Kuijpers M, Wulf PS, Keijzer N, Demmers J, Kapitein LC, Jaarsma D, Gerritsen HC, Akhmanova A, and Hoogenraad CC. TRAK/Milton motor-adaptor proteins steer mitochondrial trafficking to axons and dendrites. Neuron. 2013 Feb 6, 77(3): 485-502. PMID: 23395375.

2012

van der Vaart B, Franker MA, Kuijpers M, Hua S, Bouchet BP, Jiang K, Grigoriev I, Hoogenraad CC, and Akhmanova A. Microtubule plus-end tracking proteins SLAIN1/2 and ch-TOG promote axonal development. J Neurosci. 2012 Oct 17, 32(42): 14722-8. PMID: 23077057.

Splinter D, Razafsky DS, Schlager MA, Serra-Marques A, Grigoriev I, Demmers J, Keijzer N, Jiang K, Poser I, Hyman AA, Hoogenraad CC, King SJ, Akhmanova A.BICD2, dynactin and LIS1 cooperate in regulating dynein recruitment to cellular structures. Mol Biol Cell. 2012 Sep 5.PMID:22956769

Jiang K, Toedt G, Montenegro Gouveia S, Davey NE, Hua S, van der Vaart B, Grigoriev I, Larsen J, Pedersen LB, Bezstarosti K, Lince-Faria M, Demmers J, Steinmetz MO, Gibson TJ, Akhmanova A. A Proteome-wide Screen for Mammalian SxIP Motif-Containing Microtubule Plus-End Tracking Proteins. Curr Biol. 2012 Oct 9;22(19):1800-7. PMID:22885064

Louwen R, Nieuwenhuis EE, van Marrewijk L, Horst-Kreft D, de Ruiter L, Heikema AP, van Wamel WJ, Wagenaar JA, Endtz HP, Samsom J, van Baarlen P, Akhmanova A, van Belkum A. Campylobacter jejuni translocation across intestinal epithelial cells is facilitated by ganglioside-like lipooligosaccharide structures. Infect Immun. 2012 Sep;80(9):3307-18. PMID:22778098

Ratheesh A, Gomez GA, Priya R, Verma S, Kovacs EM, Jiang K, Brown NH, Akhmanova A, Stehbens SJ, Yap AS. Centralspindlin and α-catenin regulate Rho signalling at the epithelial zonula adherens. Nat Cell Biol. 2012 Aug;14(8):818-28. PMID:22750944

Lui-Roberts WW, Stinchcombe JC, Ritter AT, Akhmanova A, Karakesisoglou I, Griffiths GM. Cytotoxic T lymphocyte effector function is independent of nucleus-centrosome dissociation. Eur J Immunol. 2012 Aug;42(8):2132-41. PMID: 22736282

Buey RM, Sen I, Kortt O, Mohan R, Gfeller D, Veprintsev D, Kretzschmar I, Scheuermann J, Neri D, Zoete V, Michielin O, de Pereda JM, Akhmanova A, Volkmer R, Steinmetz MO. Sequence determinants of a microtubule tip localization signal (MtLS). J Biol Chem. 2012 Aug 17;287(34):28227-42. PMID: 22696216 

Pagano A, Honoré S, Mohan R, Berges R, Akhmanova A, Braguer D.Epothilone B inhibits migration of glioblastoma cells by inducing microtubule catastrophes and affecting EB1 accumulation at microtubule plus ends. Biochem Pharmacol. 2012 Aug 15;84(4):432-43. PMID:22634050

Huveneers S, Oldenburg J, Spanjaard E, van der Krogt G, Grigoriev I, Akhmanova A, Rehmann H, de Rooij J. Vinculin associates with endothelial VE-cadherin junctions to control force-dependent remodeling. J Cell Biol. 2012 Mar 5;196(5):641-52. PMID: 22391038

2011

Lomakin AJ, Kraikivski P, Semenova I, Ikeda K, Zaliapin I, Tirnauer JS, Akhmanova A, Rodionov V. Stimulation of the CLIP-170--dependent capture of membrane organelles by microtubules through fine tuning of microtubule assembly dynamics. Mol Biol Cell. 2011 Nov;22(21):4029-37. Epub 2011 Aug 31. PMID:  21880898

Tanenbaum ME, Macurek L, van der Vaart B, Galli M, Akhmanova A, Medema RH. A complex of Kif18b and MCAK promotes microtubule depolymerization and is negatively regulated by Aurora kinases.Curr Biol. 2011 Aug 23;21(16):1356-65. Epub 2011 Aug 4. PMID: 21820309

Kovacs EM, Verma S, Ali RG, Ratheesh A, Hamilton NA, Akhmanova A, Yap AS. N-WASP regulates the epithelial junctional actin cytoskeleton through a non-canonical post-nucleation pathway. Nat Cell Biol. 2011 Jul 24. doi: 10.1038/ncb2290. PMID: 21785420

van der Vaart B, Manatschal C, Grigoriev I, Olieric V, Gouveia SM, Bjelic S, Demmers J, Vorobjev I, Hoogenraad CC, Steinmetz MO, Akhmanova A. SLAIN2 links microtubule plus end-tracking proteins and controls microtubule growth in interphase. J Cell Biol. 2011 Jun 13;193(6):1083-99. Epub 2011 Jun 6.PMID: 21646404

Grigoriev I, Yu KL, Martinez-Sanchez E, Serra-Marques A, Smal I, Meijering E, Demmers J, Peränen J, Pasterkamp RJ, van der Sluijs P, Hoogenraad CC, Akhmanova A.Rab6, Rab8, and MICAL3 cooperate in controlling docking and fusion of exocytotic carriers. Curr Biol. 2011 Jun 7;21(11):967-74. Epub 2011 May 19. PMID: 21596566

Schrøder JM, Larsen J, Komarova Y, Akhmanova A, Thorsteinsson RI, Grigoriev I, Manguso R, Christensen ST, Pedersen SF, Geimer S, Pedersen LB. EB1 and EB3 promote cilia biogenesis by several centrosome-related mechanisms. J Cell Sci. 2011 Aug 1;124(Pt 15):2539-51.PMID:21768326

Buey RM, Mohan R, Leslie K, Walzthoeni T, Missimer JH, Menzel A, Bjelic S, Bargsten K, Grigoriev I, Smal I, Meijering E, Aebersold R, Akhmanova A, Steinmetz MO. Insights into EB structure and the role of its C-terminal domain in discriminating microtubule tips from lattice. Mol Biol Cell. 2011 Jul 7.PMID: 21737692

Kapitein LC, Yau KW, Gouveia SM, van der Zwan WA, Wulf PS, Keijzer N, Demmers J, Jaworski J, Akhmanova A, Hoogenraad CC.NMDA receptor activation suppresses microtubule growth and spine entry. J Neurosci. 2011 Jun 1;31(22):8194-209. PMID:21632941

Spangler SA, Jaarsma D, de Graaff E, Wulf PS, Akhmanova A, Hoogenraad CC. Differential expression of liprin-α family proteins in the brain suggests functional diversification. J Comp Neurol. 2011 May 25. doi: 10.1002/cne.22665. PMID:21618222

2010

Montenegro Gouveia S, Leslie K, Kapitein LC, Buey RM, Grigoriev I, Wagenbach M, Smal I, Meijering E, Hoogenraad CC, Wordeman L, Steinmetz MO, Akhmanova A. In vitro reconstitution of the functional interplay between MCAK and EB3 at microtubule plus ends. Curr Biol. 2010 Oct 12;20(19):1717-22. Epub 2010 Sep 16.PMID:20850319

Splinter D, Tanenbaum ME, Lindqvist A, Jaarsma D, Flotho A, Yu KL, Grigoriev I, Engelsma D, Haasdijk ED, Keijzer N, Demmers J, Fornerod M, Melchior F, Hoogenraad CC, Medema RH, Akhmanova A. Bicaudal D2, dynein, and kinesin-1 associate with nuclear pore complexes and regulate centrosome and nuclear positioning during mitotic entry.PLoS Biol. 2010 Apr 6;8(4):e1000350.PMID: 20386726

Lee HS, Komarova YA, Nadezhdina ES, Anjum R, Peloquin JG, Schober JM, Danciu O, van Haren J, Galjart N, Gygi SP, Akhmanova A, Borisy GG.Phosphorylation controls autoinhibition of cytoplasmic linker protein-170.Mol Biol Cell. 2010 Aug 1;21(15):2661-73. Epub 2010 Jun 2. PMID:20519438

Hotta A, Kawakatsu T, Nakatani T, Sato T, Matsui C, Sukezane T, Akagi T, Hamaji T, Grigoriev I, Akhmanova A, Takai Y, Mimori-Kiyosue Y. Laminin-based cell adhesion anchors microtubule plus ends to the epithelial cell basal cortex through LL5alpha/beta.J Cell Biol. 2010 May 31;189(5):901-17.PMID:20513769

Schlager MA, Kapitein LC, Grigoriev I, Burzynski GM, Wulf PS, Keijzer N, de Graaff E, Fukuda M, Shepherd IT, Akhmanova A, Hoogenraad CC. Pericentrosomal targeting of Rab6 secretory vesicles by Bicaudal-D-related protein 1 (BICDR-1) regulates neuritogenesis. EMBO J. 2010 May 19;29(10):1637-51. Epub 2010 Apr 1. PMID:20360680

Smal I, Grigoriev I, Akhmanova A, Niessen WJ, Meijering E.Microtubule dynamics analysis using kymographs and variable-rate particle filters.IEEE Trans Image Process. 2010 Jul;19(7):1861-76. Epub 2010 Mar 11.PMID:20227980

De Groot CO, Jelesarov I, Damberger FF, Bjelic S, Schaerer MA, Bhavesh NS, Grigoriev I, Buey RM, Wuthrich K, Capitani G, Akhmanova A, Steinmetz MO. Molecular insights into mammalian end binding protein heterodimerization. J Biol Chem. 2010 Feb 19;285(8):5802-14. Epub 2009 Dec 12. PMID: 20008324 PubMed

2009

Smal I, Grigoriev I, Akhmanova A, Niessen WJ, Meijering E. Accurate estimation of microtubule dynamics using kymographs and variable-rate particle filters. Conf Proc IEEE Eng Med Biol Soc. 2009;1:1012-5. PMID: 19963986 PubMed

Lomakin AJ, Semenova I, Zaliapin I, Kraikivski P, Nadezhdina E, Slepchenko BM, Akhmanova A, Rodionov V. CLIP-170-dependent capture of membrane organelles by microtubules initiates minus-end directed transport. Dev Cell. 2009 Sep;17(3):323-33. PMID: 19758557 PubMed

Honnappa S, Gouveia SM, Weisbrich A, Damberger FF, Bhavesh NS, Jawhari H, Grigoriev I, van Rijssel FJ, Buey RM, Lawera A, Jelesarov I, Winkler FK, Wüthrich K, Akhmanova A, Steinmetz MO. An EB1-binding motif acts as a microtubule tip localization signal. Cell. 2009 Jul 23;138(2):366-76. PMID: 19632184 PubMed

Komarova Y, De Groot CO, Grigoriev I, Gouveia SM, Munteanu EL, Schober JM, Honnappa S, Buey RM, Hoogenraad CC, Dogterom M, Borisy GG, Steinmetz MO, Akhmanova A. Mammalian end binding proteins control persistent microtubule growth. J Cell Biol. 2009 Mar 9;184(5):691-706. Epub 2009 Mar 2. PMID: 19255245 PubMed

Jaworski J, Kapitein LC, Gouveia SM, Dortland BR, Wulf PS, Grigoriev I, Camera P, Spangler SA, Di Stefano P, Demmers J, Krugers H, Defilippi P, Akhmanova A, Hoogenraad CC. Dynamic microtubules regulate dendritic spine morphology and synaptic plasticity. Neuron. 2009 Jan 15;61(1):85-100. PMID: 19146815 PubMed

2008

Teuling E, van Dis V, Wulf PS, Haasdijk ED, Akhmanova A, Hoogenraad CC, Jaarsma D. A novel mouse model with impaired dynein/dynactin function develops amyotrophic lateral sclerosis (ALS)-like features in motor neurons and improves lifespan in SOD1-ALS mice. Hum Mol Genet. 2008 Sep 15;17(18):2849-62. Epub 2008 Jun 25. PMID: 18579581 PubMed

Smal I, Meijering E, Draegestein K, Galjart N, Grigoriev I, Akhmanova A, van Royen ME, Houtsmuller AB, Niessen W. Multiple object tracking in molecular bioimaging by Rao-Blackwellized marginal particle filtering. Med Image Anal. 2008 Dec;12(6):764-77. Epub 2008 Mar 31. PMID: 18457985 [PubMed - indexed for MEDLINE]

Dhonukshe P, Grigoriev I, Fischer R, Tominaga M, Robinson DG, Hasek J, Paciorek T, Petrásek J, Seifertová D, Tejos R, Meisel LA, Zazímalová E, Gadella TW Jr, Stierhof YD, Ueda T, Oiwa K, Akhmanova A, Brock R, Spang A, Friml J. Auxin transport inhibitors impair vesicle motility and actin cytoskeleton dynamics in diverse eukaryotes. Proc Natl Acad Sci U S A. 2008 Mar 18;105(11):4489-94. Epub 2008 Mar 12. PMID: 18337510 PubMed

Grigoriev I, Gouveia SM, van der Vaart B, Demmers J, Smyth JT, Honnappa S, Splinter D, Steinmetz MO, Putney JW Jr, Hoogenraad CC, Akhmanova A. STIM1 Is a MT-Plus-End-Tracking Protein Involved in Remodeling of the ER. Curr Biol. 2008 Feb 12;18(3):177-82. Epub 2008 Jan 31. PMID: 18249114 PubMed

Dragestein KA, van Cappellen WA, van Haren J, Tsibidis GD, Akhmanova A, Knoch TA, Grosveld F, Galjart N. Dynamic behavior of GFP-CLIP-170 reveals fast protein turnover on microtubule plus ends. J Cell Biol. 2008 Feb 25;180(4):729-37. Epub 2008 Feb 18. PMID: 18283108 PubMed

2007

Grigoriev I, Splinter D, Keijzer N, Wulf PS, Demmers J, Ohtsuka T, Modesti M, Maly IV, Grosveld F, Hoogenraad CC, Akhmanova A. Rab6 regulates transport and targeting of exocytotic carriers. Dev Cell. 2007 Aug;13(2):305-14. PMID: 17681140 PubMed

Weisbrich A, Honnappa S, Jaussi R, Okhrimenko O, Frey D, Jelesarov I, Akhmanova A, Steinmetz MO. Structure-function relationship of CAP-Gly domains. Nat Struct Mol Biol. 2007 Oct;14(10):959-67. Epub 2007 Sep 9. PMID: 17828277 PubMed

Teuling E, Ahmed S, Haasdijk E, Demmers J, Steinmetz MO, Akhmanova A, Jaarsma D, Hoogenraad CC. Motor neuron disease-associated mutant vesicle-associated membrane protein-associated protein (VAP) B recruits wild-type VAPs into endoplasmic reticulum-derived tubular aggregates. J Neurosci. 2007 Sep 5;27(36):9801-15. PMID: 17804640 PubMed

Wanschers BF, van de Vorstenbosch R, Schlager MA, Splinter D, Akhmanova A, Hoogenraad CC, Wieringa B, Fransen JA. A role for the Rab6B Bicaudal-D1 interaction in retrograde transport in neuronal cells. Exp Cell Res. 2007 Oct 1;313(16):3408-20. Epub 2007 Jul 17. PMID: 17707369 PubMed

Efimov A, Kharitonov A, Efimova N, Loncarek J, Miller PM, Andreyeva N, Gleeson P, Galjart N, Maia AR, McLeod IX, Yates JR 3rd, Maiato H, Khodjakov A, Akhmanova A, Kaverina I. Asymmetric CLASP-dependent nucleation of noncentrosomal microtubules at the trans-Golgi network. Dev Cell. 2007 Jun;12(6):917-30. PMID: 17543864 PubMed

Schober JM, Komarova YA, Chaga OY, Akhmanova A, Borisy GG. Microtubule-targeting-dependent reorganization of filopodia. J Cell Sci. 2007 Apr 1;120(Pt 7):1235-44. Epub 2007 Mar 13. PMID: 17356063 PubMed

Tsvetkov AS, Samsonov A, Akhmanova A, Galjart N, Popov SV. Microtubule-binding proteins CLASP1 and CLASP2 interact with actin filaments. Cell Motil Cytoskeleton. 2007 Jul;64(7):519-30. PMID: 17342765 PubMed

2006

Lansbergen G, Grigoriev I, Mimori-Kiyosue Y, Ohtsuka T, Higa S, Kitajima I, Demmers J, Galjart N, Houtsmuller AB, Grosveld F, Akhmanova A. CLASPs attach microtubule plus ends to the cell cortex through a complex with LL5beta. Dev Cell. 2006 Jul;11(1):21-32. PMID: 16824950 PubMed

Drabek K, van Ham M, Stepanova T, Draegestein K, van Horssen R, Sayas CL, Akhmanova A, Ten Hagen T, Smits R, Fodde R, Grosveld F, Galjart N. Role of CLASP2 in microtubule stabilization and the regulation of persistent motility. Curr Biol. 2006 Nov 21;16(22):2259-64. PMID: 17113391 PubMed

Mimori-Kiyosue Y, Grigoriev I, Sasaki H, Matsui C, Akhmanova A, Tsukita S, Vorobjev I. Mammalian CLASPs are required for mitotic spindle organization and kinetochore alignment. Genes Cells. 2006 Aug;11(8):845-57. PMID: 16866869 PubMed

Stehbens SJ, Paterson AD, Crampton MS, Shewan AM, Ferguson C, Akhmanova A, Parton RG, Yap AS.  Dynamic microtubules regulate the local concentration of E-cadherin at cell-cell contacts. J Cell Sci. 2006 May 1;119(Pt 9):1801-11. Epub 2006 Apr 11. PMID: 16608875 PubMed

 

2005

Akhmanova A, Mausset-Bonnefont AL, van Cappellen W, Keijzer N, Hoogenraad CC, Stepanova T, Drabek K, van der Wees J, Mommaas M, Onderwater J, van der Meulen H, Tanenbaum ME, Medema RH, Hoogerbrugge J, Vreeburg J, Uringa EJ, Grootegoed JA, Grosveld F, Galjart N. The microtubule plus-end-tracking protein CLIP-170 associates with the spermatid manchette and is essential for spermatogenesis. Genes Dev. 2005 Oct 15;19(20):2501-15. PMID: 16230537 PubMed

Komarova Y, Lansbergen G, Galjart N, Grosveld F, Borisy GG, Akhmanova A. EB1 and EB3 control CLIP dissociation from the ends of growing microtubules. Mol Biol Cell. 2005 Nov;16(11):5334-45. Epub 2005 Sep 7. PMID: 16148041
PubMed

Mimori-Kiyosue Y, Grigoriev I, Lansbergen G, Sasaki H, Matsui C, Severin F, Galjart N, Grosveld F, Vorobjev I, Tsukita S, Akhmanova A. CLASP1 and CLASP2 bind to EB1 and regulate microtubule plus-end dynamics at the cell cortex. J Cell Biol. 2005 Jan 3;168(1):141-53.  PMID: 15631994
PubMed

2004

Lansbergen G, Komarova Y, Modesti M, Wyman C, Hoogenraad CC, Goodson HV, Lemaitre RP, Drechsel DN, van Munster E, Gadella TW Jr, Grosveld F, Galjart N, Borisy GG, Akhmanova A. Conformational changes in CLIP-170 regulate its binding to microtubules and dynactin localization. J Cell Biol. 2004 Sep 27;166(7):1003-14. Epub 2004 Sep 20. PMID: 15381688 PubMed

2003

Hoogenraad CC, Wulf P, Schiefermeier N, Stepanova T, Galjart N, Small JV, Grosveld F, de Zeeuw CI, Akhmanova A. Bicaudal D induces selective dynein-mediated microtubule minus end-directed transport. EMBO J. 2003 Nov 17;22(22):6004-15. PMID: 14609947 PubMed

Stepanova T, Slemmer J, Hoogenraad CC, Lansbergen G, Dortland B, De Zeeuw CI, Grosveld F, van Cappellen G, Akhmanova A, Galjart N. Visualization of microtubule growth in cultured neurons via the use of EB3-GFP (end-binding protein 3-green fluorescent protein). J Neurosci. 2003 Apr 1;23(7):2655-64. PMID: 12684451
PubMed

2002

Matanis T, Akhmanova A, Wulf P, Del Nery E, Weide T, Stepanova T, Galjart N, Grosveld F, Goud B, De Zeeuw CI, Barnekow A, Hoogenraad CC. Bicaudal-D regulates COPI-independent Golgi-ER transport by recruiting the dynein-dynactin motor complex. Nat Cell Biol. 2002 Dec;4(12):986-92. Erratum in: Nat Cell Biol. 2003 Jan;5(1):84. PMID: 12447383 PubMed

Komarova YA, Akhmanova AS, Kojima S, Galjart N, Borisy GG. Cytoplasmic linker proteins promote microtubule rescue in vivo. J Cell Biol. 2002 Nov 25;159(4):589-99. PMID: 12446741
PubMed

Hoogenraad CC, Koekkoek B, Akhmanova A, Krugers H, Dortland B, Miedema M, van Alphen A, Kistler WM, Jaegle M, Koutsourakis M, Van Camp N, Verhoye M, van der Linden A, Kaverina I, Grosveld F, De Zeeuw CI, Galjart N. Targeted mutation of Cyln2 in the Williams syndrome critical region links CLIP-115 haploinsufficiency to neurodevelopmental abnormalities in mice. Nat Genet. 2002 Sep;32(1):116 27. Epub 2002 Aug 26. Erratum in: Nat Genet 2002 Oct;32(2):331. PMID: 12195424
PubMed

Coquelle FM, Caspi M, Cordelieres FP, Dompierre JP, Dujardin DL, Koifman C, Martin P, Hoogenraad CC, Akhmanova A, Galjart N, De Mey JR, Reiner O. LIS1, CLIP-170's key to the dynein/dynactin pathway. Mol Cell Biol. 2002 May;22(9):3089-102. PMID: 11940666
PubMed

2001

Hoogenraad CC, Akhmanova A, Howell SA, Dortland BR, De Zeeuw CI, Willemsen R, Visser P, Grosveld F, Galjart N. Mammalian Golgi-associated Bicaudal-D2 functions in the dynein-dynactin pathway by interacting with these complexes. EMBO J. 2001 Aug 1;20(15):4041-54. PMID: 11483508 PubMed

Akhmanova A, Hoogenraad CC, Drabek K, Stepanova T, Dortland B, Verkerk T, Vermeulen W, Burgering BM, De Zeeuw CI, Grosveld F, Galjart N. Clasps are CLIP-115 and -170 associating proteins involved in the regional regulation of microtubule dynamics in motile fibroblasts. Cell. 2001 Mar 23;104(6):923-35. PMID: 11290329
PubMed

2000

Akhmanova A, Verkerk T, Langeveld A, Grosveld F, Galjart N. Characterisation of transcriptionally active and inactive chromatin domains in neurons. J Cell Sci. 2000 Dec;113 Pt 24:4463-74. PMID: 11082040 PubMed

Hoogenraad CC, Akhmanova A, Grosveld F, De Zeeuw CI, Galjart N. Functional analysis of CLIP-115 and its binding to microtubules. J Cell Sci. 2000 Jun;113 ( Pt 12):2285-97. PMID: 10825300
PubMed

 

 Reviews

2013

Larsen J, Grigoriev I, Akhmanova A, and Pedersen LB. Analysis of microtubule plus-end-tracking proteins in cilia. Methods Enzymol. 2013, 524: 105-22. PMID: 23498737.

Akhmanova A and Stearns T. Cell architecture: putting the building blocks together. Curr Opin Cell Biol. 2013 Feb, 25(1): 3-5. PMID: 23279910

2011

Akhmanova A, Dogterom M.Kinesins lead aging microtubules to catastrophe. Cell. 2011 Nov 23;147(5):966-8. PMID:22118452

Tanenbaum ME, Medema RH, Akhmanova A. Regulation of localization and activity of the microtubule depolymerase MCAK. Bioarchitecture. 2011 Mar;1(2):80-87. PMID: 21866268

Akhmanova A, Steinmetz MO. Microtubule end binding: EBs sense the guanine nucleotide state. Curr Biol. 2011 Apr 26;21(8):R283-5. PMID:21514511

Yu KL, Keijzer N, Hoogenraad CC, Akhmanova A. Isolation of Novel +TIPs and Their Binding Partners Using Affinity Purification Techniques. Methods Mol Biol. 2011;777:293-316.PMID:21773937

Tanenbaum ME, Akhmanova A, Medema RH. Bi-directional transport of the nucleus by dynein and kinesin-1. Commun Integr Biol. 2011 Jan;4(1):21-5.PMID:21509171

Jiang K, Akhmanova A. Microtubule tip-interacting proteins: a view from both ends. Curr Opin Cell Biol. 2011 Feb;23(1):94-101. PMID: 20817499

2010

Hoogenraad CC, Akhmanova A. Dendritic spine plasticity: new regulatory roles of dynamic microtubules.Neuroscientist. 2010 Dec;16(6):650-61.PMID: 21239729

Gouveia SM, Akhmanova A. Cell and molecular biology of microtubule plus end tracking proteins: end binding proteins and their partners. Int Rev Cell Mol Biol. 2010;285:1-74. Review. PMID: 21035097

Akhmanova A, Steinmetz MO. Microtubule +TIPs at a glance. J Cell Sci. 2010 Oct 15;123(Pt 20):3415-9. Review. No abstract available. PMID: 20930136

Tanenbaum ME, Akhmanova A, Medema RH. Dynein at the nuclear envelope. EMBO Rep. 2010 Sep;11(9):649. PMID: 20805838

Grigoriev I, Akhmanova A. Microtubule dynamics at the cell cortex probed by TIRF microscopy. Methods Cell Biol. 2010;97:91-109. Review. PMID: 20719267

Akhmanova A, Hammer JA 3rd. Linking molecular motors to membrane cargo.Curr Opin Cell Biol. 2010 Aug;22(4):479-87. Epub 2010 May 11. Review. PMID: 20466533

2009

van der Vaart B, Akhmanova A, Straube A. Regulation of microtubule dynamic instability. Biochem Soc Trans. 2009 Oct;37(Pt 5):1007-13. Review. PMID: 19754441 PubMed

Stehbens SJ, Akhmanova A, Yap AS. Microtubules and cadherins: a neglected partnership. Front Biosci. 2009 Jan 1;14:3159-67. Review. PMID: 19273264 PubMed

Akhmanova A, Stehbens SJ, Yap AS. Touch, grasp, deliver and control: functional cross-talk between microtubules and cell adhesions. Traffic. 2009 Mar;10(3):268-74. Epub 2009 Jan 17. Review. PMID: 19175539 PubMed

2008

Akhmanova A, Yap AS. Organizing junctions at the cell-cell interface. Cell. 2008 Nov 28;135(5):791-3. PMID: 19041742 PubMed

Steinmetz MO, Akhmanova A. Capturing protein tails by CAP-Gly domains. Trends Biochem Sci. 2008 Nov;33(11):535-45. Epub 2008 Oct 4. Review. PMID: 18835717 PubMed

Akhmanova A, Steinmetz MO. Tracking the ends: a dynamic protein network controls the fate of microtubule tips. Nat Rev Mol Cell Biol. 2008 Mar 5; [Epub ahead of print] PMID: 18322465 PubMed

2007

Jaworski J, Hoogenraad CC, Akhmanova A. Microtubule plus-end tracking proteins in differentiated mammalian cells. Int J Biochem Cell Biol. 2007 Oct 22; [Epub ahead of print] PMID: 18023603 PubMed

2006

Lansbergen G, Akhmanova A. Microtubule plus end: a hub of cellular activities. Traffic. 2006 May;7(5):499-507. PMID: 16643273 PubMed

2005

Akhmanova A, Hoogenraad CC. Microtubule plus-end-tracking proteins: mechanisms and functions. Curr Opin Cell Biol. 2005 Feb;17(1):47-54. Review. PMID: 15661518 PubMed

2004

Akhmanova A, Severin F. Thirteen is the lucky number for doublecortin. Dev Cell. 2004 Jul;7(1):5-6. Review. PMID: 15239948 PubMed

Hoogenraad CC, Akhmanova A, Galjart N, De Zeeuw CI. LIMK1 and CLIP-115: linking cytoskeletal defects to Williams syndrome. Bioessays. 2004 Feb;26(2):141-50. Review. PMID: 14745832 PubMed