Synaptotagmin-7 outperforms synaptotagmin-1 to promote the formation of large, stable fusion pores via robust membrane penetration.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
27 Nov 2023
27 Nov 2023
Historique:
received:
23
01
2023
accepted:
11
10
2023
medline:
29
11
2023
pubmed:
28
11
2023
entrez:
27
11
2023
Statut:
epublish
Résumé
Synaptotagmin-1 and synaptotagmin-7 are two prominent calcium sensors that regulate exocytosis in neuronal and neuroendocrine cells. Upon binding calcium, both proteins partially penetrate lipid bilayers that bear anionic phospholipids, but the specific underlying mechanisms that enable them to trigger exocytosis remain controversial. Here, we examine the biophysical properties of these two synaptotagmin isoforms and compare their interactions with phospholipid membranes. We discover that synaptotagmin-1-membrane interactions are greatly influenced by membrane order; tight packing of phosphatidylserine inhibits binding due to impaired membrane penetration. In contrast, synaptotagmin-7 exhibits robust membrane binding and penetration activity regardless of phospholipid acyl chain structure. Thus, synaptotagmin-7 is a super-penetrator. We exploit these observations to specifically isolate and examine the role of membrane penetration in synaptotagmin function. Using nanodisc-black lipid membrane electrophysiology, we demonstrate that membrane penetration is a critical component that underlies how synaptotagmin proteins regulate reconstituted, exocytic fusion pores in response to calcium.
Identifiants
pubmed: 38012142
doi: 10.1038/s41467-023-42497-8
pii: 10.1038/s41467-023-42497-8
pmc: PMC10681989
doi:
Substances chimiques
Synaptotagmins
134193-27-4
Calcium
SY7Q814VUP
Synaptotagmin I
0
Calcium-Binding Proteins
0
Phospholipids
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
7761Subventions
Organisme : NIMH NIH HHS
ID : R01 MH061876
Pays : United States
Organisme : NINDS NIH HHS
ID : R35 NS097362
Pays : United States
Informations de copyright
© 2023. The Author(s).
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