title: Diverse trafficking abnormalities of connexin32 mutants causing CMTX.
abstract: Mutations in GJB1, the gene encoding the gap junction protein connexin32 (Cx32), cause X-linked Charcot-Marie-Tooth disease (CMTX). We compared the localization of CMTX mutants that affect different domains of Cx32, by expressing them in HeLa cells. Mutants were localized to the endoplasmic reticulum (M34K, N205I, and Y211x), in the Golgi apparatus without reaching the cell membrane (M34T, V38M, A40V, R75Q, R75P, R75W, and C217x), in the Golgi apparatus but also forming rare small gap junction-like plaques (M34I, M34V, and V37M), or mainly on the cell membrane, forming gap junction-like plaques (V35M, I213V, R219C, R219H, R220G, R230C, R230L, R238H, L239I, and S281x). Selected mutants expressed in cultured rat Schwann cells showed localization similar to that in HeLa cells. Thus, many CMTX mutants have trafficking abnormalities, whereas the carboxy-terminus mutants reach the cell membrane and probably cause disease through other mechanisms.
authors.affiliation: Division of Neurology, St. Christopher's Hospital for Children, MCP--Hahnemann University, Philadelphia, Pennsylvania 19134, USA.
authors.forename: Sabrina W
authors.initials: SW
authors.lastname: Yum
authors.forename: Kleopas A
authors.initials: KA
authors.lastname: Kleopa
authors.forename: Susan
authors.initials: S
authors.lastname: Shumas
authors.forename: Steven S
authors.initials: SS
authors.lastname: Scherer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002607:Charcot-Marie-Tooth Disease / Q000235:genetics / Q000378:metabolism*; D017630:Connexins / Q000737:chemistry / Q000235:genetics*; D017629:Gap Junctions / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D021381:Protein Transport / Q000502:physiology; D051381:Rats; D012583:Schwann Cells / Q000166:cytology / Q000378:metabolism; D012584:Sciatic Nerve / Q000166:cytology; D014960:X Chromosome; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D000097002:Gap Junction beta-1 Protein