The C2A domain of synaptotagmin is an essential component of the calcium sensor for synaptic transmission.
Amino Acid Sequence
Animals
Animals, Genetically Modified
/ metabolism
Calcium
/ metabolism
Drosophila
/ growth & development
Drosophila Proteins
/ chemistry
Excitatory Postsynaptic Potentials
Humans
Larva
/ metabolism
Mutagenesis, Site-Directed
Neuromuscular Junction
/ metabolism
Neurotransmitter Agents
/ metabolism
Protein Binding
Protein Domains
Protein Structure, Tertiary
Sequence Alignment
Synaptic Transmission
Synaptotagmins
/ chemistry
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2020
2020
Historique:
received:
22
11
2019
accepted:
13
01
2020
entrez:
8
2
2020
pubmed:
8
2
2020
medline:
25
4
2020
Statut:
epublish
Résumé
The synaptic vesicle protein, synaptotagmin, is the principle Ca2+ sensor for synaptic transmission. Ca2+ influx into active nerve terminals is translated into neurotransmitter release by Ca2+ binding to synaptotagmin's tandem C2 domains, triggering the fast, synchronous fusion of multiple synaptic vesicles. Two hydrophobic residues, shown to mediate Ca2+-dependent membrane insertion of these C2 domains, are required for this process. Previous research suggested that one of its tandem C2 domains (C2B) is critical for fusion, while the other domain (C2A) plays only a facilitatory role. However, the function of the two hydrophobic residues in C2A have not been adequately tested in vivo. Here we show that these two hydrophobic residues are absolutely required for synaptotagmin to trigger vesicle fusion. Using in vivo electrophysiological recording at the Drosophila larval neuromuscular junction, we found that mutation of these two key C2A hydrophobic residues almost completely abolished neurotransmitter release. Significantly, mutation of both hydrophobic residues resulted in more severe deficits than those seen in synaptotagmin null mutants. Thus, we report the most severe phenotype of a C2A mutation to date, demonstrating that the C2A domain is absolutely essential for synaptotagmin's function as the electrostatic switch.
Identifiants
pubmed: 32032373
doi: 10.1371/journal.pone.0228348
pii: PONE-D-19-32484
pmc: PMC7006929
doi:
Substances chimiques
Drosophila Proteins
0
Neurotransmitter Agents
0
Synaptotagmins
134193-27-4
Calcium
SY7Q814VUP
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0228348Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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