Valosin-containing protein, VCP, is a ubiquitous clathrin-binding protein

Abstract

CLATHRIN is the structural protein of coated membranes involved in receptor-mediated endocytosis and aspects of Golgi sorting in eukaryotic cells. We have now detected a stoichiometric complex of clathrin with a novel protein of M_r ~100,000 (100K) in lysates of different mammalian cells. Formation of the complex, which also includes the 70K heat-shock protein HscTO, occurs within 15 min of synthesis. The 100K protein has been identified as valosin-containing protein (VCP; ref. 1), an early substrate for tyrosine phosphorylation on T-cell receptor activation². Further, VCP is the mammalian homologue of yeast Cdc48p (ref. 3) and is a member of a larger gene family that includes putative ATP-binding proteins involved in vesicle transport and fusion^4,5, 26S proteasome function⁶, regulation of the expression of human immunodeficiency virus^7,8, and assembly of peroxisomes⁹. The association with clathrin and the morphological and catalytic similarity to the chaperonin proteins indicate that VCP may modulate protein-protein interactions in membrane transport processes.