VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission

Jesica Raingo, Mikhail Khvotchev, Pei Liu, Frederic Darios, Ying C. Li, Denise M O Ramirez, Megumi Adachi, Philippe Lemieux, Katalin Toth, Bazbek Davletov, Ege T. Kavalali

Research output: Contribution to journalArticle

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Abstract

Synaptic vesicles in the brain harbor several soluble N-ethylmaleimide- sensitive-factor attachment protein receptor (SNARE) proteins. With the exception of synaptobrevin2, or VAMP2 (syb2), which is directly involved in vesicle fusion, the role of these SNAREs in neurotransmission is unclear. Here we show that in mice syb2 drives rapid Ca 2+ -dependent synchronous neurotransmission, whereas the structurally homologous SNARE protein VAMP4 selectively maintains bulk Ca 2+ -dependent asynchronous release. At inhibitory nerve terminals, up- or downregulation of VAMP4 causes a correlated change in asynchronous release. Biochemically, VAMP4 forms a stable complex with SNAREs syntaxin-1 and SNAP-25 that does not interact with complexins or synaptotagmin-1, proteins essential for synchronous neurotransmission. Optical imaging of individual synapses indicates that trafficking of VAMP4 and syb2 show minimal overlap. Taken together, these findings suggest that VAMP4 and syb2 diverge functionally, traffic independently and support distinct forms of neurotransmission. These results provide molecular insight into how synapses diversify their release properties by taking advantage of distinct synaptic vesicle-associated SNAREs.

Original languageEnglish (US)
Pages (from-to)738-745
Number of pages8
JournalNature Neuroscience
Volume15
Issue number5
DOIs
StatePublished - May 2012

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Synaptic Vesicles
SNARE Proteins
Synaptic Transmission
Synapses
Proteins
Synaptotagmin I
Vesicle-Associated Membrane Protein 2
Syntaxin 1
Optical Imaging
Up-Regulation
Down-Regulation
Brain

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission. / Raingo, Jesica; Khvotchev, Mikhail; Liu, Pei; Darios, Frederic; Li, Ying C.; Ramirez, Denise M O; Adachi, Megumi; Lemieux, Philippe; Toth, Katalin; Davletov, Bazbek; Kavalali, Ege T.

In: Nature Neuroscience, Vol. 15, No. 5, 05.2012, p. 738-745.

Research output: Contribution to journalArticle

Raingo, J, Khvotchev, M, Liu, P, Darios, F, Li, YC, Ramirez, DMO, Adachi, M, Lemieux, P, Toth, K, Davletov, B & Kavalali, ET 2012, 'VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission', Nature Neuroscience, vol. 15, no. 5, pp. 738-745. https://doi.org/10.1038/nn.3067
Raingo, Jesica ; Khvotchev, Mikhail ; Liu, Pei ; Darios, Frederic ; Li, Ying C. ; Ramirez, Denise M O ; Adachi, Megumi ; Lemieux, Philippe ; Toth, Katalin ; Davletov, Bazbek ; Kavalali, Ege T. / VAMP4 directs synaptic vesicles to a pool that selectively maintains asynchronous neurotransmission. In: Nature Neuroscience. 2012 ; Vol. 15, No. 5. pp. 738-745.
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