title: Altered trafficking of mutant connexin32.
abstract: We examined the cellular localization of nine different connexin32 (Cx32) mutants associated with X-linked Charcot-Marie-Tooth disease (CMTX) in communication-incompetent mammalian cells. Cx32 mRNA was made, but little or no protein was detected in one class of mutants. In another class of mutants, Cx32 protein was detectable in the cytoplasm and at the cell surface, where it appeared as plaques and punctate staining. Cx32 immunoreactivity in a third class of mutants was restricted to the cytoplasm, where it often colocalized with the Golgi apparatus. Our studies suggest that CMTX mutations have a predominant effect on the trafficking of Cx32 protein, resulting in a potentially toxic cytoplasmic accumulation of Cx32 in these cells. These results and evidence of cytoplasmic accumulation of other mutated myelin proteins suggest that diseases affecting myelinating cells may share a common pathophysiology.
authors.affiliation: Department of Neurology, University of Pennsylvania Medical Center, Philadelphia, Pennsylvania 19104, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Deschênes
authors.forename: J L
authors.initials: JL
authors.lastname: Walcott
authors.forename: T L
authors.initials: TL
authors.lastname: Wexler
authors.forename: S S
authors.initials: SS
authors.lastname: Scherer
authors.forename: K H
authors.initials: KH
authors.lastname: Fischbeck
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport; D002478:Cells, Cultured; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D005786:Gene Expression Regulation; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010641:Phenotype; D017354:Point Mutation; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D017384:Sequence Deletion; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D011993:Recombinant Fusion Proteins; D000097002:Gap Junction beta-1 Protein