Functional analysis of connexin-32 mutants associated with X-linked dominant Charcot-Marie-Tooth disease

Hung Li Wang, Wen Teng Chang, Tu Hsueh Yeh, Tony Wu, Mei Shin Chen, Ching Yi Wu

Research output: Contribution to journalArticle

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Abstract

To investigate the pathogenic role of connexin-32 (Cx32) mutation in X-linked dominant Charcot-Marie-Tooth disease (CMTX), dual whole-cell voltage-clamp recordings and tracer coupling were performed to investigate functional properties of wild-type and 22 CMTX mutant Cx32 proteins expressed in N2A cells. Ten mutant Cx32 proteins either formed defective junctional channels (Y65C, V95M, R107W, L156R, R164W and G199R) or failed to form gap junctions (G12S, S182T, E208K and Y211stop). Except (G12S) and (E208K) mutants, other mutant Cx32 proteins were localized in the cell membrane despite their impaired ability to form functional gap junctions. Twelve CMTX mutations (V13L, R15Q, R22Q, I30N, V35M, V63I, R75Q, Q80R, W133R, P158A, P172S and N205S) did not affect the ability of Cx32 to form homotypic gap junctions in N2A cells. Our results indicate that 10 of 22 CMTX Cx32 mutations studied in the present investigation could lead to the assembly of defective Cx32 gap junctions, which in turn may result in peripheral neuropathy. However, further studies are required to elucidate the exact mechanism by which CMTX mutant Cx32 proteins, which retain the ability to form homotypic junctional channels, damage Schwann cells and cause demyelinating neuropathy.

Original languageEnglish
Pages (from-to)361-370
Number of pages10
JournalNeurobiology of Disease
Volume15
Issue number2
DOIs
Publication statusPublished - Mar 1 2004
Externally publishedYes

Fingerprint

Charcot-Marie-Tooth Disease
Gap Junctions
Mutation
Proteins
connexin 32
Schwann Cells
Peripheral Nervous System Diseases
Cell Membrane

Keywords

  • Connexin-32
  • Gap junction
  • Junctional conductance
  • N2A cells
  • Tracer coupling
  • X-linked dominant Charcot-Marie-Tooth disease

ASJC Scopus subject areas

  • Neurology

Cite this

Functional analysis of connexin-32 mutants associated with X-linked dominant Charcot-Marie-Tooth disease. / Wang, Hung Li; Chang, Wen Teng; Yeh, Tu Hsueh; Wu, Tony; Chen, Mei Shin; Wu, Ching Yi.

In: Neurobiology of Disease, Vol. 15, No. 2, 01.03.2004, p. 361-370.

Research output: Contribution to journalArticle

Wang, Hung Li ; Chang, Wen Teng ; Yeh, Tu Hsueh ; Wu, Tony ; Chen, Mei Shin ; Wu, Ching Yi. / Functional analysis of connexin-32 mutants associated with X-linked dominant Charcot-Marie-Tooth disease. In: Neurobiology of Disease. 2004 ; Vol. 15, No. 2. pp. 361-370.
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