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.
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
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
J. Biol. Chem.
Date: Jan. 14, 2000
PubMed ID: 10625663
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