Alternative splicing of SNAP-25 regulates secretion through nonconservative substitutions in the SNARE domain.
Details
Serval ID
serval:BIB_FDCF59A9ECEA
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Alternative splicing of SNAP-25 regulates secretion through nonconservative substitutions in the SNARE domain.
Journal
Molecular Biology of the Cell
ISSN
1059-1524 (Print)
ISSN-L
1059-1524
Publication state
Published
Issued date
2005
Peer-reviewed
Oui
Volume
16
Number
12
Pages
5675-5685
Language
english
Abstract
The essential membrane fusion apparatus in mammalian cells, the soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) complex, consists of four alpha-helices formed by three proteins: SNAP-25, syntaxin 1, and synaptobrevin 2. SNAP-25 contributes two helices to the complex and is targeted to the plasma membrane by palmitoylation of four cysteines in the linker region. It is alternatively spliced into two forms, SNAP-25a and SNAP-25b, differing by nine amino acids substitutions. When expressed in chromaffin cells from SNAP-25 null mice, the isoforms support different levels of secretion. Here, we investigated the basis of that different secretory phenotype. We found that two nonconservative substitutions in the N-terminal SNARE domain and not the different localization of one palmitoylated cysteine cause the functional difference between the isoforms. Biochemical and molecular dynamic simulation experiments revealed that the two substitutions do not regulate secretion by affecting the property of SNARE complex itself, but rather make the SNAP-25b-containing SNARE complex more available for the interaction with accessory factor(s).
Keywords
Alternative Splicing, Amino Acid Sequence, Amino Acid Substitution, Animals, Chromaffin Cells/physiology, Circular Dichroism, Computer Simulation, Exons/genetics, Mice, Mice, Knockout, Molecular Sequence Data, SNARE Proteins/chemistry, SNARE Proteins/genetics, Synaptosomal-Associated Protein 25/chemistry, Synaptosomal-Associated Protein 25/deficiency
Pubmed
Web of science
Create date
15/09/2011 9:22
Last modification date
20/08/2019 17:28