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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 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 Ca(2+)-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.

Pubmed ID: 10625663 RIS Download

Mesh terms: Adaptor Proteins, Vesicular Transport | Amino Acid Sequence | Animals | Brain | Calcium | Carrier Proteins | Cloning, Molecular | Exocytosis | Gene Expression Regulation | Gene Library | Hippocampus | Membrane Proteins | Molecular Sequence Data | Molecular Weight | Nerve Tissue Proteins | Organ Specificity | PC12 Cells | Protein Conformation | Protein Structure, Secondary | Rats | Recombinant Proteins | Subcellular Fractions | Synaptosomal-Associated Protein 25 | Transfection | Vesicular Transport Proteins

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Associated grants

  • Agency: NINDS NIH HHS, Id: NS37939

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