Selective interactions of UPIa and UPIb, two members of the transmembrane 4 superfamily, with distinct single transmembrane-domained proteins in differentiated urothelial cells.

摘要: The transmembrane 4 (TM4) superfamily contains many important leukocyte differentiation-related surface proteins including CD9, CD37, CD53, and CD81; tumor-associated antigens CD63/ME491, CO-029, SAS; a newly identified metastasis suppressor gene R2. Relatively little is known, however, about the structure aggregation state of these four transmembrane-domained proteins. asymmetrical unit membrane (AUM), believed to play major role in stabilizing apical mammalian urothelium thus preventing it from rupturing during bladder distention, two TM4 members, uroplakins (UPs) Ia Ib. In association with other (single transmembrane-domained) proteins, UPII UPIII, UPIa UPIb form 16-nm particles that naturally two-dimensional crystalline arrays, providing unique opportunities for studying function. To better understand how interact particles, we analyzed their nearest neighbor relationship by chemical cross-linking. We show here UPIb, which share 39% amino acid sequence, are cross-linked respectively. also has propensity oligomerize, forming complexes stable SDS, can be readily homodimers. formation homodimers sensitive, octyl glucoside solubilize AUMs. These data suggest there exist types AUM contain UPIa/UPII or UPIb/UPIII, support model occupy inner outer domains, respectively, particle. This account apparent "redundancy" uroplakins, as structurally related interacting different partners, may roles formation. suggests plaques uroplakin compositions differ assembly, abilities an underlying cytoskeleton. Our indicate closely present same cell, distinct partners. provides excellent system targeting, processing, assembly