Functional analysis of connexin-26 mutants associated with hereditary recessive deafness

Hung Li Wang, Wen Teng Chang, Allen H. Li, Tu Hsueh Yeh, Ching Yi Wu, Mei Shin Chen, Pei Chen Huang

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

The physiological importance of connexin-26 (Cx26) gap junctions in regulating auditory function is indicated by the finding that autosomal recessive DFNB1 deafness is associated with mutations of the Cx26 gene. To investigate the pathogenic role of Cx26 mutation in recessive hearing loss, four putative DFNB1 Cx26 mutants (V84L, V95M, R127H, and R143W) were stably expressed in N2A cells, a communication-deficient cell line. In N2A cells expressing (R127H) Cx26 gap junctions, macroscopic junctional conductance and ability of transferring neurobiotin between transfected cells were greatly reduced. Despite the formation of defective junctional channels, immunoreactivity of (R127H) Cx26 was mainly localized in the cell membrane and prominent in the region of cell-cell contact. Mutant (V84L), (V95M), or (R143W) Cx26 protein formed gap junctions with a junctional conductance similar to that of wild-type Cx26 junctional channels. (V84L), (V95M), or (R143W) Cx26 gap junctions also permitted neurobiotin transfer between pairs of transfected N2A cells. The present study suggests that (R127H) mutation associated with hereditary sensorineural deafness results in the formation of defective Cx26 gap junctions, which may lead to the malfunction of cochlear gap junctions and hearing loss. Further studies are required to determine the exact mechanism by which mutant (V84L), (V95M), and (R143W) Cx26 proteins, which are capable of forming functional homotypic junctional channels in N2A cells, cause the cochlear dysfunction and sensorineural deafness.

Original languageEnglish
Pages (from-to)735-742
Number of pages8
JournalJournal of Neurochemistry
Volume84
Issue number4
DOIs
Publication statusPublished - Feb 1 2003
Externally publishedYes

Keywords

  • Connexin-26
  • DFNB1 recessive deafness
  • Gap junction
  • Junctional conductance
  • N2A cells
  • Tracer coupling

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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