TY - JOUR
T1 - Vti1a Identifies a Vesicle Pool that Preferentially Recycles at Rest and Maintains Spontaneous Neurotransmission
AU - Ramirez, Denise M O
AU - Khvotchev, Mikhail
AU - Trauterman, Brent
AU - Kavalali, Ege T.
N1 - Funding Information:
This work is supported by grants from the NIMH (R01MH066198) to E.T.K. and (F32MH093109) to D.M.O.R. We thank Dr. Thomas C. Südhof for his encouragement and support at the initial stages of this work. We thank Drs. Megumi Adachi and Pei Liu for assistance with syb2 knockout mice. We also thank Dr. Thierry Galli for the initial VAMP7 expression construct and Drs. Matthew Kennedy and Michael Ehlers for the TfR-pHluorin construct. We greatly appreciate Dr. Christopher Gilpin's help with immuno-EM analysis and Dr. Manjot Bal sharing syntaxin6-expressing neurons. We gratefully acknowledge Dr. Lisa M. Monteggia for discussions and her critical insight during this project.
PY - 2012/1/12
Y1 - 2012/1/12
N2 - Recent studies suggest that synaptic vesicles (SVs) giving rise to spontaneous neurotransmission are distinct from those that carry out evoked release. However, the molecular basis of this dichotomy remains unclear. Here, we focused on two noncanonical SNARE molecules, Vps10p-tail-interactor-1a (vti1a) and VAMP7, previously shown to reside on SVs. Using simultaneous multicolor imaging at individual synapses, we could show that compared to the more abundant vesicular SNARE synaptobrevin2, both vti1a and VAMP7 were reluctantly mobilized during activity. Vti1a, but not VAMP7, showed robust trafficking under resting conditions that could be partly matched by synaptobrevin2. Furthermore, loss of vti1a function selectively reduced high-frequency spontaneous neurotransmitter release detected postsynaptically. Expression of a truncated version of vti1a augmented spontaneous release more than full-length vti1a, suggesting that an autoinhibitory process regulates vti1a function. Taken together, these results support the premise that in its native form vti1a selectively maintains spontaneous neurotransmitter release. Recent studies suggest that synaptic vesicles giving rise to spontaneous neurotransmission are distinct from those that carry out evoked release. Ramirez etal. address the role of the synaptic vesicle-associated SNARE protein vti1a and demonstrate a selective role for this protein in spontaneous neurotransmitter release.
AB - Recent studies suggest that synaptic vesicles (SVs) giving rise to spontaneous neurotransmission are distinct from those that carry out evoked release. However, the molecular basis of this dichotomy remains unclear. Here, we focused on two noncanonical SNARE molecules, Vps10p-tail-interactor-1a (vti1a) and VAMP7, previously shown to reside on SVs. Using simultaneous multicolor imaging at individual synapses, we could show that compared to the more abundant vesicular SNARE synaptobrevin2, both vti1a and VAMP7 were reluctantly mobilized during activity. Vti1a, but not VAMP7, showed robust trafficking under resting conditions that could be partly matched by synaptobrevin2. Furthermore, loss of vti1a function selectively reduced high-frequency spontaneous neurotransmitter release detected postsynaptically. Expression of a truncated version of vti1a augmented spontaneous release more than full-length vti1a, suggesting that an autoinhibitory process regulates vti1a function. Taken together, these results support the premise that in its native form vti1a selectively maintains spontaneous neurotransmitter release. Recent studies suggest that synaptic vesicles giving rise to spontaneous neurotransmission are distinct from those that carry out evoked release. Ramirez etal. address the role of the synaptic vesicle-associated SNARE protein vti1a and demonstrate a selective role for this protein in spontaneous neurotransmitter release.
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U2 - 10.1016/j.neuron.2011.10.034
DO - 10.1016/j.neuron.2011.10.034
M3 - Article
C2 - 22243751
AN - SCOPUS:84855748925
SN - 0896-6273
VL - 73
SP - 121
EP - 134
JO - Neuron
JF - Neuron
IS - 1
ER -