气候变化领域集成服务门户(CCPortal): Neuromodulator release in neurons requires two functionally redundant calcium sensors

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DOI	10.1073/pnas.2012137118
	Neuromodulator release in neurons requires two functionally redundant calcium sensors
	van Westen R.; Poppinga J.; Arazola R.D.; Toonen R.F.; Verhage M.
发表日期	2021
ISSN	0027-8424
卷号	118 期号:18
英文摘要	Neuropeptides and neurotrophic factors secreted from dense core vesicles (DCVs) control many brain functions, but the calcium sensors that trigger their secretion remain unknown. Here, we show that in mouse hippocampal neurons, DCV fusion is strongly and equally reduced in synaptotagmin-1 (Syt1)- or Syt7-deficient neurons, but combined Syt1/Syt7 deficiency did not reduce fusion further. Cross-rescue, expression of Syt1 in Syt7-deficient neurons, or vice versa, completely restored fusion. Hence, both sensors are rate limiting, operating in a single pathway. Overexpression of either sensor in wild-type neurons confirmed this and increased fusion. Syt1 traveled with DCVs and was present on fusing DCVs, but Syt7 supported fusion largely from other locations. Finally, the duration of single DCV fusion events was reduced in Syt1-deficient but not Syt7-deficient neurons. In conclusion, two functionally redundant calcium sensors drive neuromodulator secretion in an expression-dependent manner. In addition, Syt1 has a unique role in regulating fusion pore duration. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Dense core vesicles; Hippocampal neurons; Neuromodulators; Synaptotagmin-1; Synaptotagmin-7
语种	英语
scopus关键词	synaptotagmin; synaptotagmin 7; synaptotagmin I; unclassified drug; agents interacting with transmitter, hormone or drug receptors; calcium; nerve growth factor; neuropeptide; synaptotagmin; synaptotagmin I; Syt1 protein, mouse; Syt7 protein, mouse; animal cell; Article; brain nerve cell; C57BL 6 mouse; cell organelle; cellular distribution; controlled study; dense core vesicle; female; hippocampus; latent period; male; mouse; nerve cell membrane potential; neuromodulation; nonhuman; priority journal; protein expression; synapse; wild type; animal; brain; chemistry; gene expression regulation; genetics; human; metabolism; nerve cell; pathology; Animals; Brain; Calcium; Dense Core Vesicles; Gene Expression Regulation; Hippocampus; Humans; Mice; Nerve Growth Factors; Neurons; Neuropeptides; Neurotransmitter Agents; Synaptotagmin I; Synaptotagmins
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/251198
作者单位	Department of Functional Genomics, Center for Neurogenomics and Cognitive Research, Neuroscience Campus Amsterdam, Vrije Universiteit Amsterdam, Amsterdam, 1081 HV, Netherlands; Department of Clinical Genetics, Amsterdam University Medical Centers, Amsterdam, 1081 HV, Netherlands
推荐引用方式 GB/T 7714	van Westen R.,Poppinga J.,Arazola R.D.,et al. Neuromodulator release in neurons requires two functionally redundant calcium sensors[J],2021,118(18).
APA	van Westen R.,Poppinga J.,Arazola R.D.,Toonen R.F.,&Verhage M..(2021).Neuromodulator release in neurons requires two functionally redundant calcium sensors.Proceedings of the National Academy of Sciences of the United States of America,118(18).
MLA	van Westen R.,et al."Neuromodulator release in neurons requires two functionally redundant calcium sensors".Proceedings of the National Academy of Sciences of the United States of America 118.18(2021).