VAP-A Binds Promiscuously to both v- and tSNAREs

• Published in: Biochemical and biophysical research communications 2001-08, Vol.286 (3), p.616-621
• Main Authors: Weir, M.Lynn, Xie, Hong, Klip, Amira, Trimble, William S.
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Surface - metabolism; Carrier Proteins - chemistry; Carrier Proteins - metabolism; Cell Line; COS Cells; 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
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.2001.5437

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, αSNAP, 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.