The interaction between Shroom3 and Rho-kinase is required for neural tube morphogenesis in mice.
The interaction between Shroom3 and Rho-kinase is required for neural tube morphogenesis in mice.
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DOI：
10.1242/bio.20147450
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发表时间：
2014-08-29
期刊：
影响因子：
2.4
通讯作者：
Hildebrand JD
中科院分区：
文献类型：
--
作者：
Das D;Zalewski JK;Mohan S;Plageman TF;VanDemark AP;Hildebrand JD
Shroom3是一种肌动蛋白相关的细胞形态调节因子，是小鼠神经管闭合、透镜基板形成和肠道形态发生所必需的，并与人类慢性肾脏疾病和定向心脏循环有关。许多研究表明Shroom3可能通过直接结合Rho激酶并促进顶端定位的收缩性肌动球蛋白网络的组装来调节这些发育过程。我们已经表征了由ENU诱导的突变引起的神经管缺陷的分子基础，所述突变导致小鼠Shroom3的位置1838处的精氨酸至半胱氨酸氨基酸取代。我们表明，这种取代对Shroom3的表达或定位没有影响，但消除了Rock结合，并使Shroom3对调节细胞形态的能力无功能。我们的研究结果表明，Rock是Shroom3在神经管形态发生过程中的主要下游效应子。基于序列保守性和生物化学分析，我们预测，蘑菇岩石相互作用是高度保守的动物进化，并代表了一个信号模块，用于各种生物过程。
Shroom3 is an actin-associated regulator of cell morphology that is required for neural tube closure, formation of the lens placode, and gut morphogenesis in mice and has been linked to chronic kidney disease and directional heart looping in humans. Numerous studies have shown that Shroom3 likely regulates these developmental processes by directly binding to Rho-kinase and facilitating the assembly of apically positioned contractile actomyosin networks. We have characterized the molecular basis for the neural tube defects caused by an ENU-induced mutation that results in an arginine-to-cysteine amino acid substitution at position 1838 of mouse Shroom3. We show that this substitution has no effect on Shroom3 expression or localization but ablates Rock binding and renders Shroom3 non-functional for the ability to regulate cell morphology. Our results indicate that Rock is the major downstream effector of Shroom3 in the process of neural tube morphogenesis. Based on sequence conservation and biochemical analysis, we predict that the Shroom-Rock interaction is highly conserved across animal evolution and represents a signaling module that is utilized in a variety of biological processes.
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