v-SNARE Composition Distinguishes Synaptic Vesicle Pools

Department of Neurology, University of California, San Francisco School of Medicine, San Francisco, CA 94143, USA.
Neuron (Impact Factor: 15.05). 08/2011; 71(3):474-87. DOI: 10.1016/j.neuron.2011.06.010
Source: PubMed


Synaptic vesicles belong to two distinct pools, a recycling pool responsible for the evoked release of neurotransmitter and a resting pool unresponsive to stimulation. The uniform appearance of synaptic vesicles has suggested that differences in location or cytoskeletal association account for these differences in function. We now find that the v-SNARE tetanus toxin-insensitive vesicle-associated membrane protein (VAMP7) differs from other synaptic vesicle proteins in its distribution to the two pools, providing evidence that they differ in molecular composition. We also find that both resting and recycling pools undergo spontaneous release, and when activated by deletion of the longin domain, VAMP7 influences the properties of release. Further, the endocytosis that follows evoked and spontaneous release differs in mechanism, and specific sequences confer targeting to the different vesicle pools. The results suggest that different endocytic mechanisms generate synaptic vesicles with different proteins that can endow the vesicles with distinct properties.

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    • "This task is inherently more complex as SVs are homogenous in size and display a defined protein and lipid composition that can only be maintained by high fidelity adaptor-mediated sorting processes that serve to ''proofread'' SV composition. This task may be further complicated by the existence of functionally distinct pools of vesicles that may display compositional heterogeneity (Hua et al., 2011b; Raingo et al., 2012; Ramirez et al., 2012). However, CME as well as endosomal pathways of vesicle budding employed to reform functional SVs operate on a timescale of tens of seconds and, thus, provide a potential kinetic bottleneck when used for compensatory membrane retrieval at synapses undergoing high rates of firing. "
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