VAP-A binds promiscuously to both v- and tSNAREs.
Proteins that bind to SNAREs may regulate their function. One such protein, VAP-33, was first discovered in Aplysia californica and has two mammalian homologues, VAP-A and VAP-B. VAP-A has been implicated in vesicle targeting to the plasma membrane based on its location in polarized cells and its ability to bind VAMP in vitro. Here, we demonstrate that VAP-A is a widely expressed resident of the ER/Golgi intermediate compartment in COS-7 cells. Moreover, we demonstrate that VAMP-binding and VAP-dimerization require both the N- and C-terminal domains of VAP-A and also that VAP-A binds to a wide range of SNAREs and fusion-related proteins including syntaxin 1A, rbet1, rsec22, alphaSNAP, and NSF. Together, these results suggest that VAP-A is not a regulator of a specific VAMP, but rather may play a more general role in SNARE-mediated vesicle traffic between the ER and Golgi in nonpolarized cells.
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Programme in Cell Biology, Department of Biochemistry, Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, Ontario, M5G 1X8, Canada.
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D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D019556:COS Cells; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism*; D002460:Cell Line; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D052066:N-Ethylmaleimide-Sensitive Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism; D050767:Qc-SNARE Proteins; D050683:R-SNARE Proteins; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; D050827:Syntaxin 1; D014018:Tissue Distribution; D022161:Transport Vesicles / Q000378:metabolism*; D033921:Vesicular Transport Proteins
D000954:Antigens, Surface; C098783:BET1 protein, rat; D002352:Carrier Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D050767:Qc-SNARE Proteins; D050683:R-SNARE Proteins; C484373:SEC22A protein, human; C494212:STX1A protein, human; D052067:Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins; C494213:Stx1a protein, rat; D050827:Syntaxin 1; C114051:VAPA protein, human; C491919:Vapa protein, rat; D033921:Vesicular Transport Proteins; D052066:N-Ethylmaleimide-Sensitive Proteins; C498737:Nsf protein, rat