VAP-A binds promiscuously to both v- and tSNAREs

Biochem Biophys Res Commun. 2001 Aug 24;286(3):616-21. doi: 10.1006/bbrc.2001.5437.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Surface / metabolism
  • COS Cells
  • Carrier Proteins / chemistry
  • Carrier Proteins / metabolism*
  • Cell Line
  • Dimerization
  • Endoplasmic Reticulum / metabolism
  • Golgi Apparatus / metabolism
  • Humans
  • Membrane Proteins / chemistry
  • Membrane Proteins / metabolism*
  • N-Ethylmaleimide-Sensitive Proteins
  • Nerve Tissue Proteins / metabolism
  • Qc-SNARE Proteins
  • R-SNARE Proteins
  • Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
  • Syntaxin 1
  • Tissue Distribution
  • Transport Vesicles / metabolism*
  • Vesicular Transport Proteins*

Substances

  • Antigens, Surface
  • BET1 protein, rat
  • Carrier Proteins
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Qc-SNARE Proteins
  • R-SNARE Proteins
  • SEC22A protein, human
  • STX1A protein, human
  • Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins
  • Stx1a protein, rat
  • Syntaxin 1
  • VAPA protein, human
  • Vapa protein, rat
  • Vesicular Transport Proteins
  • N-Ethylmaleimide-Sensitive Proteins
  • Nsf protein, rat