Neuromodulator release in neurons requires two functionally redundant calcium sensors.
Animals
Brain
/ metabolism
Calcium
/ chemistry
Dense Core Vesicles
/ genetics
Gene Expression Regulation
/ genetics
Hippocampus
/ metabolism
Humans
Mice
Nerve Growth Factors
/ chemistry
Neurons
/ metabolism
Neuropeptides
/ chemistry
Neurotransmitter Agents
/ chemistry
Synaptotagmin I
/ genetics
Synaptotagmins
/ genetics
dense core vesicles
hippocampal neurons
neuromodulators
synaptotagmin-1
synaptotagmin-7
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
04 05 2021
04 05 2021
Historique:
entrez:
27
4
2021
pubmed:
28
4
2021
medline:
15
12
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33903230
pii: 2012137118
doi: 10.1073/pnas.2012137118
pmc: PMC8106342
pii:
doi:
Substances chimiques
Nerve Growth Factors
0
Neuropeptides
0
Neurotransmitter Agents
0
Synaptotagmin I
0
Syt1 protein, mouse
0
Syt7 protein, mouse
0
Synaptotagmins
134193-27-4
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare no competing interest.
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