ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles.
ROCK-I regulates closure of the eyelids and ventral body wall by inducing assembly of actomyosin bundles.
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DOI：
10.1083/jcb.200411179
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发表时间：
2005-03-14
期刊：
影响因子：
--
通讯作者：
Narumiya S
中科院分区：
文献类型：
--
作者：
Shimizu Y;Thumkeo D;Keel J;Ishizaki T;Oshima H;Oshima M;Noda Y;Matsumura F;Taketo MM;Narumiya S
Rho相关激酶(ROCK)I介导从Rho到肌动蛋白细胞骨架的信号传递。为了研究ROCK-I的体内功能，我们建立了ROCK-I缺陷小鼠。ROCK-I的丢失导致眼皮关闭失败和腹侧体壁关闭，从而导致新生儿出生时睁眼和脐膨出表型。大多数ROCK-I−/−小鼠出生后不久就死于母亲对脐膨出的蚕食。在ROCK-I−/−胚胎中，眼睑上皮细胞中环绕眼睛的肌动蛋白绳索被打乱，脐环上丝状肌动蛋白的积聚受到损害，两个部位的肌球蛋白调节轻链都失去了磷酸化。在ROCK-I−/−小鼠的原代角质形成细胞中，表皮生长因子诱导的应力纤维形成和多层细胞角质形成细胞的磷酸化程度也被减弱。这些结果表明，ROCK-I通过肌动肌球蛋白束的组织来调节眼睑和腹侧体壁的关闭。
Rho-associated kinase (ROCK) I mediates signaling from Rho to the actin cytoskeleton. To investigate the in vivo functions of ROCK-I, we generated ROCK-I–deficient mice. Loss of ROCK-I resulted in failure of eyelid closure and closure of the ventral body wall, which gave rise to the eyes open at birth and omphalocele phenotypes in neonates. Most ROCK-I−/− mice died soon after birth as a result of cannibalization of the omphalocele by the mother. Actin cables that encircle the eye in the epithelial cells of the eyelid were disorganized and accumulation of filamentous actin at the umbilical ring was impaired, with loss of phosphorylation of the myosin regulatory light chain (MLC) at both sites, in ROCK-I−/− embryos. Stress fiber formation and MLC phosphorylation induced by EGF were also attenuated in primary keratinocytes from ROCK-I−/− mice. These results suggest that ROCK-I regulates closure of the eyelids and ventral body wall through organization of actomyosin bundles.
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