PI(4,5)P<sub>2</sub>-dependent regulation of exocytosis by amisyn, the vertebrate-specific competitor of synaptobrevin 2.

Details

Serval ID
serval:BIB_B1F61DE84A16
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
PI(4,5)P<sub>2</sub>-dependent regulation of exocytosis by amisyn, the vertebrate-specific competitor of synaptobrevin 2.
Journal
Proceedings of the National Academy of Sciences of the United States of America
Author(s)
Kondratiuk I., Jakhanwal S., Jin J., Sathyanarayanan U., Kroppen B., Pobbati A.V., Krisko A., Ashery U., Meinecke M., Jahn R., Fasshauer D., Milosevic I.
ISSN
1091-6490 (Electronic)
ISSN-L
0027-8424
Publication state
Published
Issued date
16/06/2020
Peer-reviewed
Oui
Volume
117
Number
24
Pages
13468-13479
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
The functions of nervous and neuroendocrine systems rely on fast and tightly regulated release of neurotransmitters stored in secretory vesicles through SNARE-mediated exocytosis. Few proteins, including tomosyn (STXBP5) and amisyn (STXBP6), were proposed to negatively regulate exocytosis. Little is known about amisyn, a 24-kDa brain-enriched protein with a SNARE motif. We report here that full-length amisyn forms a stable SNARE complex with syntaxin-1 and SNAP-25 through its C-terminal SNARE motif and competes with synaptobrevin-2/VAMP2 for the SNARE-complex assembly. Furthermore, amisyn contains an N-terminal pleckstrin homology domain that mediates its transient association with the plasma membrane of neurosecretory cells by binding to phospholipid PI(4,5)P <sub>2</sub> However, unlike synaptrobrevin-2, the SNARE motif of amisyn is not sufficient to account for the role of amisyn in exocytosis: Both the pleckstrin homology domain and the SNARE motif are needed for its inhibitory function. Mechanistically, amisyn interferes with the priming of secretory vesicles and the sizes of releasable vesicle pools, but not vesicle fusion properties. Our biochemical and functional analyses of this vertebrate-specific protein unveil key aspects of negative regulation of exocytosis.
Keywords
PI(4,5)P2, SNARE complex, autism spectrum disorders, exocytosis inhibition, tomosyn
Pubmed
Web of science
Create date
10/06/2020 21:59
Last modification date
02/09/2020 6:22
Usage data