Spring, a novel RING finger protein that regulates synaptic vesicle exocytosis.
The synaptosome-associated protein of 25 kDa (SNAP-25) interacts with syntaxin 1 and vesicle-associated membrane protein 2 (VAMP2) to form a ternary soluble N-ethylmaleimide-sensitive fusion protein attachment protein receptor (SNARE) complex that is essential for synaptic vesicle exocytosis. We report a novel RING finger protein, Spring, that specifically interacts with SNAP-25. Spring is exclusively expressed in brain and is concentrated at synapses. The association of Spring with SNAP-25 abolishes the ability of SNAP-25 to interact with syntaxin 1 and VAMP2 and prevents the assembly of the SNARE complex. Overexpression of Spring or its SNAP-25-interacting domain reduces Ca(2+)-dependent exocytosis from PC12 cells. These results indicate that Spring may act as a regulator of synaptic vesicle exocytosis by controlling the availability of SNAP-25 for the SNARE complex formation.
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Department of Pharmacology and Cell and Molecular Physiology, University of North Carolina School of Medicine, Chapel Hill, North Carolina 27599, USA.
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Weigel
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D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006224:Cricetinae; D018076:DNA, Complementary; D005089:Exocytosis / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D016716:PC12 Cells; D050683:R-SNARE Proteins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017386:Sequence Homology, Amino Acid; D013572:Synaptic Vesicles / Q000378:metabolism*; D050825:Synaptosomal-Associated Protein 25; D050827:Syntaxin 1; D020798:Two-Hybrid System Techniques
D000954:Antigens, Surface; D002352:Carrier Proteins; D018076:DNA, Complementary; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050683:R-SNARE Proteins; D012333:RNA, Messenger; C494210:Snap25 protein, rat; C494213:Stx1a protein, rat; D050825:Synaptosomal-Associated Protein 25; D050827:Syntaxin 1; C440031:Trim9 protein, rat; D002118:Calcium