Connexin mutations causing skin disease and deafness increase hemichannel activity and cell death when expressed in Xenopus oocytes.
Connexin mutations causing skin disease and deafness increase hemichannel activity and cell death when expressed in Xenopus oocytes.
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DOI：
10.1038/jid.2008.335
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发表时间：
2009-04
期刊：
影响因子：
--
通讯作者：
White TW
中科院分区：
文献类型：
--
作者：
Lee JR;Derosa AM;White TW
编码连接蛋白26(Cx26)的GJB2基因突变与皮肤病和遗传性耳聋有关。然而，由Cx26突变引起的皮肤病的严重程度和类型是不同的。在这里，我们探讨了Cx26 KID综合征相关突变、G12R、S17F和D50N对通道功能的影响。还检测了Cx26 N14K突变，该突变与耳聋有关，但有一种皮肤病，与KID综合征突变不同。这些蛋白均在非洲爪哇卵母细胞中表达，表达水平与野生型Cx26相当。G12R、N14K和D50N突变导致了比野生型表达细胞更大的半通道电流，但S17F突变导致半通道活性完全丧失。半通道活动的增加与细胞死亡的增加相关。这一结果可以通过细胞外培养上清液中钙离子的升高而逆转。只有成对的N14K细胞才能产生功能缝隙连接，尽管它们表现出完全丧失电压敏感性，但它们的电导水平与野生型相似。这组数据证实，异常的半通道活动是与KID综合征相关的Cx26突变的共同特征，这可能导致细胞活性和组织完整性的丧失。
Mutations in the GJB2 gene encoding Connexin26 (Cx26) have been linked to skin disorders and genetic deafness. However, the severity and type of the skin disorders caused by Cx26 mutations are heterogeneous. Here we explored the effect of Cx26 KID syndrome associated mutations, G12R, S17F, and D50N on channel function. The Cx26 N14K mutation was also examined which is associated with deafness but has a skin disorder distinct from the KID syndrome mutations. The proteins were all expressed in Xenopus oocytes with levels equal to wild-type Cx26. The G12R, N14K, and D50N mutations resulted in larger hemichannel currents than the wild-type expressing cells, but the S17F mutation resulted in a complete loss of hemichannel activity. Elevated hemichannel activity correlated with an increased cell death. This result could be reversed through the elevation of calcium (Ca2+) in the extracellular media. Functional gap junctions were only produced by paired N14K cells, which had a similar conductance level to wild-type, even though they exhibited a complete loss of voltage sensitivity. This set of data confirms that aberrant hemichannel activity is a common feature of Cx26 mutations associated with KID syndrome, and this may contribute to a loss of cell viability and tissue integrity.
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DOI：
10.1085/jgp.114.3.339
发表时间：
1999-09
期刊：
The Journal of general physiology
影响因子：
--
作者：
Oh S;Rubin JB;Bennett MV;Verselis VK;Bargiello TA
通讯作者：
Bargiello TA
影响因子：
19
作者：
Kelsell, DP;Dunlop, J;Hodgins, MB
通讯作者：
Hodgins, MB
影响因子：
13.8
作者：
Montgomery, JR;White, TW;Holland, SM
通讯作者：
Holland, SM
影响因子：
3.3
作者：
BRUZZONE, R;HAEFLIGER, JA;PAUL, DL
通讯作者：
PAUL, DL
影响因子：
3.8
作者：
Ebihara, L;Steiner, E
通讯作者：
Steiner, E