期刊
JOURNAL OF CELL SCIENCE
卷 119, 期 10, 页码 2138-2144出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/jcs.02940
关键词
gap junction; connexin; knock-in alpha 3 (KI alpha 3); cataract
类别
资金
- NEI NIH HHS [EY13849, EY013163, EY05314] Funding Source: Medline
A G22R point mutation in alpha 8 connexin (Cx50) has been previously shown to cause a severe cataract by interacting with endogenous wild-type alpha 3 connexin (Cx46) in mouse lenses. Here, we tested whether a knocked-in alpha 3 connexin expressed on the locus of the endogenous alpha 8 connexin could modulate the severe cataract caused by the alpha 8-G22R mutation. We found that the alpha 3(-/-) alpha 8(G22R/-) mice developed severe cataracts with disrupted inner fibers and posterior rupture while the alpha 3(-/-) alpha 8( G22R/KI alpha 3) lens contained relatively normal inner fibers without lens posterior rupture. The alpha 8-G22R mutant proteins produced typical punctate staining of gap junctions between fiber cells of alpha 3(-/-) alpha 8( G22R/KI alpha 3) lenses, but not in those of alpha 3(-/-) alpha 8( G22R/-) lenses. Thus, we hypothesize that the knocked-in alpha 3 connexin subunits interact with the alpha 8-G22R connexin subunits to form functional gap junction channels and rescue the lens phenotype. Using an electrical coupling assay consisting of paired Xenopus oocytes, we demonstrated that only co-expression of mutant alpha 8-G22R and wild-type alpha 3 connexin subunits forms functional gap junction channels with reduced conductance and altered voltage sensitivity compared with the channels formed by alpha 3 connexin subunits alone. Thus, knocked-in alpha 3 connexin and mutant alpha 8-G22R connexin probably form heteromeric gap junction channels that influence lens homeostasis and lens transparency.
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