Increased Hemichannel Activity Displayed by a Connexin43 Mutation Causing a Familial Connexinopathy Exhibiting Hypotrichosis with Follicular Keratosis and Hyperostosis.
Increased Hemichannel Activity Displayed by a Connexin43 Mutation Causing a Familial Connexinopathy Exhibiting Hypotrichosis with Follicular Keratosis and Hyperostosis.
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DOI：
10.3390/ijms24032222
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发表时间：
2023-01-22
影响因子：
5.6
通讯作者：
White, Thomas W.
中科院分区：
文献类型：
--
作者：
Crouthamel, Olivia E.;Li, Leping;Dilluvio, Michael T.;White, Thomas W.
编码连接蛋白43 （Cx43）的GJA1基因突变导致几种罕见的遗传疾病，包括影响表皮的疾病。在这里，我们研究了Cx43突变Cx43- g38e的体外功能后果，该突变与人类毛少症、滤泡性角化病和骨质增生的新表型有关。我们发现Cx43-G38E在非洲爪蟾卵母细胞中有效翻译，并在转染的HeLa细胞中定位于间隙连接斑块。Cx43- g38e在爪蟾卵母细胞中形成了与野生型Cx43相同效率的功能性缝隙连接通道，但缝隙连接通道的电压门控发生了改变。值得注意的是，与野生型Cx43相比，Cx43- g38e通过形成活性半通道显著增加了膜电流。这些数据表明，增加的半通道活性与与骨骼-皮肤表型相关的连接蛋白突变有关，表明增加的半通道活性可能在由人类Cx43突变引起的皮肤和骨骼疾病中发挥作用。
Mutations in the GJA1 gene that encodes connexin43 (Cx43) cause several rare genetic disorders, including diseases affecting the epidermis. Here, we examined the in vitro functional consequences of a Cx43 mutation, Cx43-G38E, linked to a novel human phenotype of hypotrichosis, follicular keratosis and hyperostosis. We found that Cx43-G38E was efficiently translated in Xenopus oocytes and localized to gap junction plaques in transfected HeLa cells. Cx43-G38E formed functional gap junction channels with the same efficiency as wild-type Cx43 in Xenopus oocytes, although voltage gating of the gap junction channels was altered. Notably, Cx43-G38E significantly increased membrane current flow through the formation of active hemichannels when compared to wild-type Cx43. These data demonstrate the association of increased hemichannel activity to a connexin mutation linked to a skeletal-cutaneous phenotype, suggesting that augmented hemichannel activity could play a role in skin and skeletal disorders caused by human Cx43 mutations.
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影响因子：
4.3
作者：
Hua R;Zhang J;Riquelme MA;Jiang JX
通讯作者：
Jiang JX
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3.3
作者：
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