Action Mechanism of Basigin, a Membrane Glycoprotein Belonging to the Immunoglobulin Superfamily

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Basigin (Bsg) is a membrane glycoprotein, which belongs to the immunoglobulin (Ig) superfamily. Bsg has two Ig-like domain in its extracellular portion. Bsg knockout mice manifested 1. many embryonic death during implantation, 2. death due to interstitial pneumonia within one month after birth, 3. failure of spermatogenesis, oocyte maturation and implantation and 4. learning and memory deficiency. Objective of this study is to elucidate 1. the role of Bsg in spermatogenesis, 2. the mechanism and biological meanings of the homo-oligomer formation of Bsg and 3. possibility of cross-talk between Bsg and embigin, a membrane glycoprotein that has a homology with Bsg.Bsg-deficient mice exhibited azoospermia with cessation of spermatogenesis at metaphase of the first meiosis. Unusual ectoplasmic specification between Sertoli cells and spermatids was detected in Bsg-deficient mice, suggesting involvement of Bsg in ectoplasmic specification. Homo-oligomer formation of Bsg took place in the same cell membrane (cis-type association). In this oligomer formation, the N-terminal Ig-like domain plays a critical role. No association was detected between Bsg and embigin.Further analyses of Bsg-deficient mice revealed a retinal dysfunction, in which both rod and cone photoreceptor cells were functionally, severely affected from early age. The photoreceptor cells then degenerated gradually and were almost ablated by 41 weeks. Strong Bsg expression was detected in the pigment epithelium.In summary, this study has revealed a mechanism of homo-oligomer formation, which may be important for Bsg action, and discovered a novel target tissue, namely the retina, where Bsg play an important role. Identification of intracellular binding proteins of Bsg and Bsg receptor is needed for further elucidation of Bsg action mechanism.