Protein quantification at the single vesicle level reveals that a subset of synaptic vesicle proteins are trafficked with high precision

Protein sorting represents a potential point of regulation in neurotransmission because it dictates the protein composition of synaptic vesicles, the organelle that mediates transmitter release. Although the average number of most vesicle proteins has been estimated using bulk biochemical approaches...

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Bibliographic Details
Published in:The Journal of neuroscience 2011-01, Vol.31 (4), p.1461-1470
Main Authors: Mutch, Sarah A, Kensel-Hammes, Patricia, Gadd, Jennifer C, Fujimoto, Bryant S, Allen, Richard W, Schiro, Perry G, Lorenz, Robert M, Kuyper, Christopher L, Kuo, Jason S, Bajjalieh, Sandra M, Chiu, Daniel T
Format: Article
Language:English
Subjects:
Animals
Brain - metabolism
In Vitro Techniques
Membrane Proteins - metabolism
Protein Transport
Rats
Rats, Sprague-Dawley
Synaptic Vesicles - metabolism
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Summary:Protein sorting represents a potential point of regulation in neurotransmission because it dictates the protein composition of synaptic vesicles, the organelle that mediates transmitter release. Although the average number of most vesicle proteins has been estimated using bulk biochemical approaches (Takamori et al., 2006), no information exists on the intervesicle variability of protein number, and thus on the precision with which proteins are sorted to vesicles. To address this, we adapted a single molecule quantification approach (Mutch et al., 2007) and used it to quantify both the average number and variance of seven integral membrane proteins in brain synaptic vesicles. We report that four vesicle proteins, SV2, the proton ATPase, Vglut1, and synaptotagmin 1, showed little intervesicle variation in number, indicating they are sorted to vesicles with high precision. In contrast, the apparent number of VAMP2/synaptobrevin 2, synaptophysin, and synaptogyrin demonstrated significant intervesicle variability. These findings place constraints on models of protein function at the synapse and raise the possibility that changes in vesicle protein expression affect vesicle composition and functioning.
ISSN:0270-6474
1529-2401
DOI:10.1523/JNEUROSCI.3805-10.2011