Abstract |
Hearing impairment (HI) affects 1/1000 children and over 2% of the aged population. We have previously reported that mutations in the gene encoding gap junction protein connexin-31 (C×31) are associated with HI. The pathological mechanism of the disease mutations remains unknown. Here, we show that expression of C×31 in the mouse inner ear is developmentally regulated with a high level in adult inner hair cells and spiral ganglion neurons that are critical for the hearing process. In transfected cells, wild type C×31 protein (C×31wt) forms functional gap junction at cell-cell-contacts. In contrast, two HI-associated C×31 mutants, C×31R180X and C×31E183K resided primarily in the ER and Golgi-like intracellular punctate structures, respectively, and failed to mediate lucifer yellow transfer. Expression of C×31 mutants but not C×31wt leads to upregulation of and increased association with the ER chaperone BiP indicating ER stress induction. Together, the HI-associated C×31 mutants are impaired in trafficking, promote ER stress, and hence lose the ability to assemble functional gap junctions. The study reveals a potential pathological mechanism of HI-associated C×31 mutations.
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Authors | Kun Xia, Hong Ma, Hui Xiong, Qian Pan, Liangqun Huang, Danling Wang, Zhuohua Zhang |
Journal | Protein & cell
(Protein Cell)
Vol. 1
Issue 10
Pg. 935-43
(Oct 2010)
ISSN: 1674-8018 [Electronic] Germany |
PMID | 21204020
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- Connexins
- connexin 31, mouse
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Topics |
- Animals
- Connexins
(genetics)
- Ear, Inner
(metabolism)
- Endoplasmic Reticulum
(physiology)
- Gap Junctions
(genetics, metabolism, physiology)
- Golgi Apparatus
(genetics, metabolism)
- Hearing Loss
(genetics, metabolism, pathology)
- Mice
- Mutation
- Neurons
(metabolism)
- Protein Transport
(genetics)
- Stress, Physiological
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