Yum Sabrina W, Kleopa Kleopas A, Shumas Susan, Scherer Steven S
Division of Neurology, St. Christopher's Hospital for Children, MCP--Hahnemann University, Philadelphia, Pennsylvania 19134, USA.
Neurobiol Dis. 2002 Oct;11(1):43-52. doi: 10.1006/nbdi.2002.0545.
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.
编码间隙连接蛋白连接蛋白32（Cx32）的基因GJB1发生突变会导致X连锁型夏科-马里-图斯病（CMTX）。我们通过在HeLa细胞中表达影响Cx32不同结构域的CMTX突变体，比较了它们的定位情况。突变体分别定位于内质网（M34K、N205I和Y211x）、高尔基体但未到达细胞膜（M34T、V38M、A40V、R75Q、R75P、R75W和C217x）、高尔基体但也形成罕见的小间隙连接样斑块（M34I、M34V和V37M），或主要定位于细胞膜并形成间隙连接样斑块（V35M、I213V、R219C、R219H、R220G、R230C、R230L、R238H、L239I和S281x）。在培养的大鼠雪旺细胞中表达的选定突变体显示出与在HeLa细胞中相似的定位。因此，许多CMTX突变体存在转运异常，而羧基末端突变体到达细胞膜并可能通过其他机制导致疾病。
