Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release.
Synaptotagmin-IV (syt-IV) is a membrane trafficking protein that influences learning and memory, but its localization and role in synaptic function remain unclear. We found that syt-IV localized to brain-derived neurotrophic factor (BDNF)-containing vesicles in hippocampal neurons. Syt-IV/BDNF-harboring vesicles underwent exocytosis in both axons and dendrites, and syt-IV inhibited BDNF release at both sites. Knockout of syt-IV increased, and overexpression decreased, the rate of synaptic vesicle exocytosis from presynaptic terminals indirectly via changes in postsynaptic release of BDNF. Thus, postsynaptic syt-IV regulates the trans-synaptic action of BDNF to control presynaptic vesicle dynamics. Furthermore, selective loss of presynaptic syt-IV increased spontaneous quantal release, whereas a loss of postsynaptic syt-IV increased quantal amplitude. Finally, syt-IV knockout mice showed enhanced long-term potentiation (LTP), which depended entirely on disinhibition of BDNF release. Thus, regulation of BDNF secretion by syt-IV emerges as a mechanism for maintaining synaptic strength in a useful range during LTP.
Dean
Camin
C
Department of Physiology, University of Wisconsin, Madison, Wisconsin, USA.
Liu
Huisheng
H
Dunning
F Mark
FM
Chang
Payne Y
PY
Jackson
Meyer B
MB
Chapman
Edwin R
ER
D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D015536:Down-Regulation / Q000235:genetics; D005089:Exocytosis / Q000235:genetics; D006624:Hippocampus / Q000378:metabolism* / Q000648:ultrastructure; D017774:Long-Term Potentiation / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D018377:Neurotransmitter Agents / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism / Q000648:ultrastructure; D055366:Synaptic Potentials / Q000235:genetics; D009435:Synaptic Transmission / Q000235:genetics*; D013572:Synaptic Vesicles / Q000378:metabolism / Q000648:ultrastructure; D050857:Synaptotagmins / Q000235:genetics / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D018377:Neurotransmitter Agents; D050857:Synaptotagmins