title: CD82 blocks cMet activation and overcomes hepatocyte growth factor effects on oligodendrocyte precursor differentiation.
abstract: Mechanisms that regulate oligodendrocyte (OL) precursor migration and differentiation are important in normal development and in demyelinating/remyelinating conditions. We previously found that the tetraspanin CD82 is far more highly expressed in O4(+) OL precursors of the adult rat brain than those of the neonatal brain. CD82 has been physically linked to cMet, the hepatocyte growth factor (HGF) receptor, in tumor cells, and this interaction decreases downstream signaling. We show here that CD82 inhibits the HGF activation of cMet in neonatal and adult rat OL precursors. CD82 expression is sufficient to allow precursor differentiation into mature OLs even in the presence of HGF. In contrast, CD82 downregulation in adult O4(+)/CD82(+) cells inhibits their differentiation, decreases their accumulation of myelin proteins, and causes a reversion to less mature stages. CD82 expression in neonatal O4(+)/CD82(-) cells also blocks Rac1 activation, suggesting a possible regulatory effect on cytoskeletal organization and mobility. Thus, CD82 is a negative regulator of HGF/cMet during OL development and overcomes HGF inhibitory regulation of OL precursor maturation.
authors: Department of Pathology and Cell Biology, Columbia University Medical Center, New York, New York 10032, USA.
authors: Angeliki
authors: A
authors: Mela
authors: James E
authors: JE
authors: Goldman
mesh_terms: D000328:Adult; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D002452:Cell Count; D002454:Cell Differentiation / Q000187:drug effects*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000235:genetics; D049452:Green Fluorescent Proteins / Q000235:genetics; D017228:Hepatocyte Growth Factor / Q000494:pharmacology*; D006801:Humans; D051861:Kangai-1 Protein / Q000378:metabolism / Q000494:pharmacology*; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000145:classification / Q000187:drug effects*
chemical_list: D051861:Kangai-1 Protein; D034741:RNA, Small Interfering; C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met
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