Trafficking abnormality and ER stress underlie functional deficiency of hearing impairment-associated connexin-31 mutants
Protein & Cell
;
(12): 935-943, 2010.
Article
in English
| WPRIM
| ID: wpr-757684
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Pathology
/
Physiology
/
Stress, Physiological
/
Gap Junctions
/
Connexins
/
Protein Transport
/
Endoplasmic Reticulum
/
Genetics
/
Golgi Apparatus
/
Hearing Loss
Limits:
Animals
Language:
English
Journal:
Protein & Cell
Year:
2010
Type:
Article
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