Synapsin selectively controls the mobility of resting pool vesicles at hippocampal terminals

Orenbuch, Ayelet, Shalev, Lee, Marra, Vincenzo, Sinai, Isaac, Lavy, Yotam, Kahn, Joy, Burden, Jemima J, Staras, Kevin and Gitler, Daniel (2012) Synapsin selectively controls the mobility of resting pool vesicles at hippocampal terminals. Journal of Neuroscience, 32 (12). pp. 3969-3980. ISSN 0270-6474

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Abstract

Presynaptic terminals are specialized sites for information transmission where vesicles fuse with the plasma membrane and are locally recycled. Recent work has extended this classical view, with the observation that a subset of functional vesicles is dynamically shared between adjacent terminals by lateral axonal transport. Conceptually, such transport would be expected to disrupt vesicle retention around the active zone, yet terminals are characterized by a high-density vesicle cluster, suggesting that counteracting stabilizing mechanisms must operate against this tendency. The synapsins are a family of proteins that associate with synaptic vesicles and determine vesicle numbers at the terminal, but their specific function remains controversial. Here, using multiple quantitative fluorescence-based approaches and electron microscopy, we show that synapsin is instrumental for resisting vesicle dispersion and serves as a regulatory element for controlling lateral vesicle sharing between synapses. Deleting synapsin disrupts the organization of presynaptic vesicle clusters, making their boundaries hard to define. Concurrently, the fraction of vesicles amenable to transport is increased, and more vesicles are translocated to the axon. Importantly, in neurons from synapsin knock-out mice the resting and recycling pools are equally mobile. Synapsin, when present, specifically restricts the mobility of resting pool vesicles without affecting the division of vesicles between these pools. Specific expression of synapsin IIa, the sole isoform affecting synaptic depression, rescues the knock-out phenotype. Together, our results show that synapsin is pivotal for maintaining synaptic vesicle cluster integrity and that it contributes to the regulated sharing of vesicles between terminals.

Item Type: Article
Schools and Departments: School of Life Sciences > Neuroscience
Subjects: Q Science > QP Physiology > QP0351 Neurophysiology and neuropsychology
Depositing User: Kevin Staras
Date Deposited: 31 Oct 2012 11:24
Last Modified: 06 Mar 2017 18:45
URI: http://sro.sussex.ac.uk/id/eprint/41044

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