OSP/claudin-11 forms a complex with a novel member of the tetraspanin super family and beta 1 integrin and regulates proliferation and migration of oligodendrocytes

Oligodendrocyte-specific protein (OSP)/claudin-11 is a major component of c entral nervous system myelin and forms tight junctions (TJs) within myelin sheaths. TJs are essential for forming a paracellular barrier and have been implicated in the regulation of growth and differentiation via signal tran sduction pathways. We have identified an OSP/claudin-11-associated protein (OAP)1, using a yeast two-hybrid screen. OAP-1 is a novel member of the tet raspanin superfamily, and it is widely expressed in several cell types, inc luding oligodendrocytes, OAP-1, OSP/claudin-11, and beta1 integrin form a c omplex as indicated by coimmunoprecipitation and confocal immunocytochemist ry. Overexpression of OSP/claudin-11 or OAP-1 induced proliferation in an o ligodendrocyte cell line. Anti-OAP-1, anti-OSP/claudin-11, and anti-beta1 i ntegrin antibodies inhibited migration of primary oligodendrocytes, and mig ration was impaired in OSP/claudin-11-deficient primary oligodendrocytes. T hese data suggest a role for OSP/claudin-11, OAP-1, and beta1 integrin comp lex in regulating proliferation and migration of oligodendrocytes, a proces s essential for normal myelination and repair.