Are you in or are you out: intracellular transport of synaptic receptors affects synaptic architecture

Researchers from Utrecht University shed light on the intracellular transport of postsynaptic receptors in neurons

In the brain, millions of neurons transfer information with each other through synapses. At the surface of an excitatory postsynapse, receptors need to be inserted with precise timing and location for the correct integration of the incoming signal from a partner axon. Postsynaptic AMPA receptors are frequently inserted and removed from the postsynaptic membrane by lateral diffusion mechanisms or intracellular transport. Although much is known about the former, less is understood of the latter. A recent joint study of the teams of Casper Hoogenraad and Lukas Kapitein at Utrecht University reveals that transport of AMPA receptors inside endosomes – vesicles involved in endo- and exocytotic events – is important for correct synaptic structure and organization.

Live cell imaging to study receptor dynamics

Making use of high resolution live cell imaging techniques, it became evident that endosomes play an important role on the insertion or removal of AMPA receptors at the synaptic surface. These may be transported within long distances or target multiple synapses, using either actin or microtubule cytoskeleton. Moreover, using a chemically inducible system, where endosomes were coupled to specific motor proteins, further elucidated the role of different cytoskeletal components in the transport of these cargos.

Removal of AMPA receptors via intracellular pathways affects synapse architecture

When coupled to Myosin-VI, an actin based motor protein, endosomes were drastically removed from the postsynapse. More detailed analysis also showed that the number of synaptic surface receptors decreased and the intracellular organization of the postsynapse was affected. Collectively, this work pushes the field towards a better understanding of the intracellular dynamics of synaptic cargo and its importance on the maintenance of synaptic architecture and function.

More information:

1. Esteves da Silva, M. Adrian, P. Schätzle, J. Lipka, T. Watanabe, S. Cho, K. Futai, C. J. Wierenga, L. C. Kapitein, C. C. Hoogenraad, Positioning of AMPA Receptor-Containing Endosomes Regulates Synapse Architecture. Cell Reports, Volume 13, Issue 5, p933-43, 03 November 2015