Type X Mutants Trafficking Abnormalities Research

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From Neurobiol Dis 2002 Oct;11(1):43-52

Diverse Trafficking Abnormalities of Connexin32 Mutants Causing CMTX

Yum SW, Kleopa KA, Shumas S, Scherer SS.

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.