Connexin 48.5 is required for normal cardiovascular function and lens development in zebrafish embryos
Connexin 48.5 is required for normal cardiovascular function and lens development in zebrafish embryos
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DOI：
10.1074/jbc.m401355200
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发表时间：
2004-08-27
影响因子：
4.8
通讯作者：
Valdimarsson, G
中科院分区：
文献类型：
--
作者：
Cheng, SH;Shakespeare, T;Valdimarsson, G
间隙连接由连接蛋白 (Cx) 蛋白组成，介导许多发育和生理过程所需的细胞间通讯。在这里，我们描述了 Cx48.5 的分离和表征，Cx48.5 是一种与哺乳动物 Cx46 具有最高序列同一性的斑马鱼连接蛋白。表达分析表明，Cx48.5 在成人和胚胎晶状体和心脏、成人睾丸中表达，并在胚胎耳囊中短暂表达。将 Cx48.5 cRNA 注射到非洲爪蟾卵母细胞中会引发细胞间电耦合，其电压敏感性与哺乳动物 Cx46 相似。在单个卵母细胞中，Cx48.5 还在去极化时诱导大的外向电流，与间隙连接半通道一致。用反义吗啉寡核苷酸（morpholinos）破坏胚胎中的 Cx48.5 表达表明，Cx48.5 在维持晶状体稳态中具有重要作用。吗啉处理过的胚胎还发育出了小晶状体和眼睛以及严重的心血管异常。
Gap junctions are composed of connexin (Cx) proteins and mediate intercellular communication required for many developmental and physiological processes. Here we describe the isolation and characterization of Cx48.5, a zebrafish connexin with the highest sequence identity to mammalian Cx46. Expression analysis showed that Cx48.5 is expressed in the adult and embryonic lens and heart, adult testis, and transiently in the embryonic otic vesicles. Injection of Cx48.5 cRNA into Xenopus oocytes elicited intercellular electrical coupling with voltage sensitivity similar to mammalian Cx46. In single oocytes, Cx48.5 also induced large outward currents on depolarization, consistent with gap-junctional hemichannels. Disruption of Cx48.5 expression in embryos with antisense morpholino oligos (morpholinos) revealed that Cx48.5 has an essential role in the maintenance of lens homeostasis. The morpholino-treated embryos also developed small lenses and eyes as well as severe cardiovascular abnormalities.