PMID- 19448629 OWN - NLM STAT- MEDLINE DCOM- 20091009 LR - 20220129 IS - 1546-1726 (Electronic) IS - 1097-6256 (Print) IS - 1097-6256 (Linking) VI - 12 IP - 6 DP - 2009 Jun TI - Synaptotagmin-IV modulates synaptic function and long-term potentiation by regulating BDNF release. PG - 767-76 LID - 10.1038/nn.2315 [doi] AB - 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. FAU - Dean, Camin AU - Dean C AD - Department of Physiology, University of Wisconsin, Madison, Wisconsin, USA. FAU - Liu, Huisheng AU - Liu H FAU - Dunning, F Mark AU - Dunning FM FAU - Chang, Payne Y AU - Chang PY FAU - Jackson, Meyer B AU - Jackson MB FAU - Chapman, Edwin R AU - Chapman ER LA - eng GR - NS44057/NS/NINDS NIH HHS/United States GR - NS049748/NS/NINDS NIH HHS/United States GR - F32 NS049748/NS/NINDS NIH HHS/United States GR - MH61876/MH/NIMH NIH HHS/United States GR - GM 56827/GM/NIGMS NIH HHS/United States GR - R01 NS044057/NS/NINDS NIH HHS/United States GR - NS30016/NS/NINDS NIH HHS/United States GR - R37 NS030016/NS/NINDS NIH HHS/United States GR - R01 GM056827/GM/NIGMS NIH HHS/United States GR - R01 MH061876/MH/NIMH NIH HHS/United States GR - HHMI/Howard Hughes Medical Institute/United States GR - R01 NS030016/NS/NINDS NIH HHS/United States GR - F32 NS049748-01A1/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't DEP - 20090517 PL - United States TA - Nat Neurosci JT - Nature neuroscience JID - 9809671 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neurotransmitter Agents) RN - 134193-27-4 (Synaptotagmins) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Dendrites/metabolism/ultrastructure MH - Down-Regulation/genetics MH - Exocytosis/genetics MH - Hippocampus/*metabolism/ultrastructure MH - Long-Term Potentiation/*genetics MH - Mice MH - Mice, Knockout MH - Neurons/*metabolism/ultrastructure MH - Neurotransmitter Agents/metabolism MH - Presynaptic Terminals/metabolism/ultrastructure MH - Synaptic Potentials/genetics MH - Synaptic Transmission/*genetics MH - Synaptic Vesicles/metabolism/ultrastructure MH - Synaptotagmins/genetics/*metabolism PMC - PMC2846764 MID - NIHMS104345 EDAT- 2009/05/19 09:00 MHDA- 2009/10/10 06:00 PMCR- 2010/03/29 CRDT- 2009/05/19 09:00 PHST- 2008/12/18 00:00 [received] PHST- 2009/03/20 00:00 [accepted] PHST- 2009/05/19 09:00 [entrez] PHST- 2009/05/19 09:00 [pubmed] PHST- 2009/10/10 06:00 [medline] PHST- 2010/03/29 00:00 [pmc-release] AID - nn.2315 [pii] AID - 10.1038/nn.2315 [doi] PST - ppublish SO - Nat Neurosci. 2009 Jun;12(6):767-76. doi: 10.1038/nn.2315. Epub 2009 May 17.