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Besides allowing ions to flow between adjacent cells, gap junctions selectively conduct larger signaling molecules. What determines their selectivity is unknown. Martinez-Wittinghan et al. (page 969) explored this problem by extensively manipulating the genetic loci of the two connexin proteins that make up gap junctions in the lens of the eye. The results show that the developing lens is exquisitely sensitive to changes in the composition of gap junctions, and that alterations in gap junction permeability could underlie human diseases ranging from cataracts to deafness.- O2 ^4 Z, S. v' E
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In previous studies, mice lacking the connexin 46 gene, which is expressed primarily in fiber cells beneath the lens epithelium, grew lenses of normal size but with severe cataracts. Deletion of the connexin 50 gene, which is expressed in both the lens epithelium and the fiber cells, caused a severe growth defect in the lens but only mild cataracts. The authors have now generated new mouse strains in which the coding sequences of connexins 46 and 50 were deleted from and swapped between their normal genetic loci in a variety of combinations, producing a spectrum of expression patterns.& m0 A6 O; W3 X6 G% m) f I5 r
6 J" _! i' P% O" N+ ^8 j$ PWhen connexins 46 and 50 are both expressed in the epithelium as well as the fiber cells, the lens grows to normal size but has severe cataracts. Expressing only connexin 46 in the epithelium and fiber cells prevents cataracts but produces a growth defect. Ionic coupling between lens cells appears to be adequate in the mutants. The authors conclude that connexin 46 maintains lens clarity, and connexin 50 ensures proper lens growth, by determining the permeability of gap junctions not just to ions but to larger biochemical signals.( s0 ^" j; l( `+ e. d
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In humans, mutations in connexin genes are associated with hearing loss, inherited cataracts, and several skin diseases. The new work suggests that these mutations might change the composition of gap junctions, altering their permeability and generating signaling errors during development.(Dye coupling (left) is sharply reduced i) |
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发表于 2009-3-6 00:51
发表于 2015-6-8 17:01
