SNIP, a Novel SNAP-25-interacting Protein Implicated in Regulated Exocytosis

Synaptosome-associated protein of 25 kDa (SNAP-25) is a presynaptic membrane protein that has been clearly implicated in membrane fusion in both developing and mature neurons, although its mechanisms of action are unclear. We have now identified a novel SNAP-25-interacting protein named SNIP. SNIP i...

Full description

Saved in:

Bibliographic Details
Published in:	The Journal of biological chemistry Vol. 275; no. 2; pp. 1191 - 1200
Main Authors:	Chin, Lih-Shen, Nugent, Russel D., Raynor, Mathew C., Vavalle, John P., Li, Lian
Format:	Journal Article
Language:	English
Published:	United States Elsevier Inc 14-01-2000 American Society for Biochemistry and Molecular Biology
Subjects:	Adaptor Proteins, Vesicular Transport Amino Acid Sequence Animals Brain - metabolism Calcium - metabolism Carrier Proteins - chemistry Carrier Proteins - genetics Carrier Proteins - metabolism Cloning, Molecular Exocytosis - physiology Gene Expression Regulation Gene Library Hippocampus - metabolism Membrane Proteins Molecular Sequence Data Molecular Weight Nerve Tissue Proteins - chemistry Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism Organ Specificity PC12 Cells Protein Conformation Protein Structure, Secondary Rats Recombinant Proteins - biosynthesis Recombinant Proteins - chemistry SNAP-25 protein SNIP protein Subcellular Fractions - metabolism Synaptosomal-Associated Protein 25 Transfection Vesicular Transport Proteins
Online Access:	Get full text
Tags:	Add Tag No Tags, Be the first to tag this record!

Description
Summary:	Synaptosome-associated protein of 25 kDa (SNAP-25) is a presynaptic membrane protein that has been clearly implicated in membrane fusion in both developing and mature neurons, although its mechanisms of action are unclear. We have now identified a novel SNAP-25-interacting protein named SNIP. SNIP is a hydrophilic, 145-kDa protein that comprises two predicted coiled-coil domains, two highly charged regions, and two proline-rich domains with multiple PPXY and PXXP motifs. SNIP is selectively expressed in brain where it co-distributes with SNAP-25 in most brain regions. Biochemical studies have revealed that SNIP is tightly associated with the brain cytoskeleton. Subcellular fractionation and immunofluorescence localization studies have demonstrated that SNIP co-localizes with SNAP-25 as well as the cortical actin cytoskeleton, suggesting that SNIP serves as a linker protein connecting SNAP-25 to the submembranous cytoskeleton. By using deletion analysis, we have mapped the binding domains of SNIP and SNAP-25, and we have demonstrated that the SNIP-SNAP-25 association is mediated via coiled-coil interactions. Moreover, we have shown that overexpression of SNIP or its SNAP-25-interacting domain inhibits Ca2+-dependent exocytosis from PC12 cells. These results indicate that SNIP is involved in regulation of neurosecretion, perhaps via its interaction with SNAP-25 and the cytoskeleton.
Bibliography:	ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2
ISSN:	0021-9258 1083-351X
DOI:	10.1074/jbc.275.2.1191