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Neuromodulator release in neurons requires two functionally redundant calcium sensors.
Neuromodulator release in neurons requires two functionally redundant calcium sensors.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2021 May 04; Vol. 118 (18). - Publication Year :
- 2021
-
Abstract
- 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.<br />Competing Interests: The authors declare no competing interest.
- Subjects :
- Animals
Calcium chemistry
Calcium metabolism
Dense Core Vesicles genetics
Dense Core Vesicles metabolism
Gene Expression Regulation genetics
Hippocampus metabolism
Humans
Mice
Nerve Growth Factors chemistry
Nerve Growth Factors metabolism
Neurons pathology
Neuropeptides chemistry
Neuropeptides metabolism
Neurotransmitter Agents metabolism
Brain metabolism
Neurons metabolism
Neurotransmitter Agents chemistry
Synaptotagmin I genetics
Synaptotagmins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1091-6490
- Volume :
- 118
- Issue :
- 18
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 33903230
- Full Text :
- https://doi.org/10.1073/pnas.2012137118