SVIP is a novel VCP/p97-interacting protein whose expression causes cell vacuolation.
VCP/p97 is involved in a variety of cellular processes, including membrane fusion and ubiquitin-dependent protein degradation. It has been suggested that adaptor proteins such as p47 and Ufd1p confer functional versatility to VCP/p97. To identify novel adaptors, we searched for proteins that interact specifically with VCP/p97 by using the yeast two-hybrid system, and discovered a novel VCP/p97-interacting protein named small VCP/p97-interacting protein (SVIP). Rat SVIP is a 76-amino acid protein that contains two putative coiled-coil regions, and potential myristoylation and palmitoylation sites at the N terminus. Binding experiments revealed that the N-terminal coiled-coil region of SVIP, and the N-terminal and subsequent ATP-binding regions (ND1 domain) of VCP/p97, interact with each other. SVIP and previously identified adaptors p47 and ufd1p interact with VCP/p97 in a mutually exclusive manner. Overexpression of full-length SVIP or a truncated mutant did not markedly affect the structure of the Golgi apparatus, but caused extensive cell vacuolation reminiscent of that seen upon the expression of VCP/p97 mutants or polyglutamine proteins in neuronal cells. The vacuoles seemed to be derived from endoplasmic reticulum membranes. These results together suggest that SVIP is a novel VCP/p97 adaptor whose function is related to the integrity of the endoplasmic reticulum.
Nagahama
Masami
M
School of Life Science, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo 192-0392, Japan.
Suzuki
Mie
M
Hamada
Yuko
Y
Hatsuzawa
Kiyotaka
K
Tani
Katsuko
K
Yamamoto
Akitsugu
A
Tagaya
Mitsuo
M
D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism*; D051381:Rats; D020798:Two-Hybrid System Techniques; D014617:Vacuoles / Q000378:metabolism*
D009687:Nuclear Proteins; D015800:Protozoan Proteins; C475849:SVIP protein, rat