Homo-oligomer formation by basigin, an immunoglobulin superfamily member, via its N-terminal immunoglobulin domain

Basigin (Bsg) is a highly glycosylated transmembrane protein with two immun oglobulin (Ig)-like domains. A number of studies, including gene targeting, have demonstrated that Bsg plays pivotal roles in spermatogenesis, implant ation, neural network formation and tumor progression. In the present study , to understand the mechanism of action of Bsg, we determined its expressio n status on the plasma membrane. Cotransfection of Bsg expression vectors w ith two different tags clarified that Bsg forms homo-oligomers in a cis-dep endent manner on the plasma membrane. If the disulfide bond of the more N-t erminally located Ig-like domain was destroyed by mutations, Bsg could not form oligomers. In contrast, the mutations of the C-terminal Ig-like domain or N-glycosylation sites did not affect the association. The association o f mouse and human Bsgs, which exhibit high homology in the transmembrane an d intracellular domains but low homology in the extracellular domain, was v ery weak as compared with that within the same species, suggesting the impo rtance of the extracellular domain in the association. If the extracellular domain of the human Ret protein was replaced with the N-terminal Ig-like d omain of Bsg, the resulting chimera protein was associated with intact wild -type Bsg, but not if the C-terminal Ig-like domain, instead of the N-termi nal one, of Bsg was used. No oligomer formation took place between the inta ct wild-type Ret and Bsg proteins. In conclusion, these data indicate that the N-terminal Ig-like domain is necessary and sufficient for oligomer form ation by Bsg on the plasma membrane.