TY - JOUR
T1 - Myosin V Regulates Spatial Localization of Different Forms of Neurotransmitter Release in Central Synapses
AU - Maschi, Dario
AU - Gramlich, Michael W.
AU - Klyachko, Vitaly A.
N1 - Funding Information:
This work was supported in part by a grant to VK from NINDS (R35 NS111596) and funds from Department of Cell Biology and Physiology at Washington University.
Funding Information:
We acknowledge the assistance of Matthew Joens and Dr. James Fitzpatrick at the Washington University Center for Cellular Imaging in EM studies. Funding. This work was supported in part by a grant to VK from NINDS (R35 NS111596) and funds from Department of Cell Biology and Physiology at Washington University.
Publisher Copyright:
© Copyright © 2021 Maschi, Gramlich and Klyachko.
PY - 2021/4/15
Y1 - 2021/4/15
N2 - Synaptic active zone (AZ) contains multiple specialized release sites for vesicle fusion. The utilization of release sites is regulated to determine spatiotemporal organization of the two main forms of synchronous release, uni-vesicular (UVR) and multi-vesicular (MVR). We previously found that the vesicle-associated molecular motor myosin V regulates temporal utilization of release sites by controlling vesicle anchoring at release sites in an activity-dependent manner. Here we show that acute inhibition of myosin V shifts preferential location of vesicle docking away from AZ center toward periphery, and results in a corresponding spatial shift in utilization of release sites during UVR. Similarly, inhibition of myosin V also reduces preferential utilization of central release sites during MVR, leading to more spatially distributed and temporally uniform MVR that occurs farther away from the AZ center. Using a modeling approach, we provide a conceptual framework that unites spatial and temporal functions of myosin V in vesicle release by controlling the gradient of release site release probability across the AZ, which in turn determines the spatiotemporal organization of both UVR and MVR. Thus myosin V regulates both temporal and spatial utilization of release sites during two main forms of synchronous release.
AB - Synaptic active zone (AZ) contains multiple specialized release sites for vesicle fusion. The utilization of release sites is regulated to determine spatiotemporal organization of the two main forms of synchronous release, uni-vesicular (UVR) and multi-vesicular (MVR). We previously found that the vesicle-associated molecular motor myosin V regulates temporal utilization of release sites by controlling vesicle anchoring at release sites in an activity-dependent manner. Here we show that acute inhibition of myosin V shifts preferential location of vesicle docking away from AZ center toward periphery, and results in a corresponding spatial shift in utilization of release sites during UVR. Similarly, inhibition of myosin V also reduces preferential utilization of central release sites during MVR, leading to more spatially distributed and temporally uniform MVR that occurs farther away from the AZ center. Using a modeling approach, we provide a conceptual framework that unites spatial and temporal functions of myosin V in vesicle release by controlling the gradient of release site release probability across the AZ, which in turn determines the spatiotemporal organization of both UVR and MVR. Thus myosin V regulates both temporal and spatial utilization of release sites during two main forms of synchronous release.
KW - active zone
KW - myosin V
KW - neurotransmitter release
KW - release probability
KW - release site
KW - synaptic transmission
KW - vesicle docking
UR - http://www.scopus.com/inward/record.url?scp=85105009467&partnerID=8YFLogxK
U2 - 10.3389/fnsyn.2021.650334
DO - 10.3389/fnsyn.2021.650334
M3 - Article
C2 - 33935678
AN - SCOPUS:85105009467
VL - 13
JO - Frontiers in Synaptic Neuroscience
JF - Frontiers in Synaptic Neuroscience
SN - 1663-3563
M1 - 650334
ER -