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顶端极性蛋白招募 RhoGEF Cysts 以促进连接肌球蛋白组装。

Apical polarity proteins recruit the RhoGEF Cysts to promote junctional myosin assembly.

机构信息

Department of Cell and Systems Biology, University of Toronto, Toronto, ON, Canada.

Department of Genetics, Harvard Medical School, Boston, MA.

出版信息

J Cell Biol. 2019 Oct 7;218(10):3397-3414. doi: 10.1083/jcb.201807106. Epub 2019 Aug 13.

DOI:10.1083/jcb.201807106
PMID:31409654
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6781438/
Abstract

The spatio-temporal regulation of small Rho GTPases is crucial for the dynamic stability of epithelial tissues. However, how RhoGTPase activity is controlled during development remains largely unknown. To explore the regulation of Rho GTPases in vivo, we analyzed the Rho GTPase guanine nucleotide exchange factor (RhoGEF) Cysts, the orthologue of mammalian p114RhoGEF, GEF-H1, p190RhoGEF, and AKAP-13. Loss of Cysts causes a phenotype that closely resembles the mutant phenotype of the apical polarity regulator Crumbs. This phenotype can be suppressed by the loss of basolateral polarity proteins, suggesting that Cysts is an integral component of the apical polarity protein network. We demonstrate that Cysts is recruited to the apico-lateral membrane through interactions with the Crumbs complex and Bazooka/Par3. Cysts activates Rho1 at adherens junctions and stabilizes junctional myosin. Junctional myosin depletion is similar in Cysts- and Crumbs-compromised embryos. Together, our findings indicate that Cysts is a downstream effector of the Crumbs complex and links apical polarity proteins to Rho1 and myosin activation at adherens junctions, supporting junctional integrity and epithelial polarity.

摘要

小 Rho GTPases 的时空调节对于上皮组织的动态稳定性至关重要。然而，RhoGTPase 活性在发育过程中是如何被控制的，在很大程度上仍然未知。为了探索体内 Rho GTPases 的调节，我们分析了 Rho GTPase 鸟嘌呤核苷酸交换因子 (RhoGEF) Cysts，其与哺乳动物 p114RhoGEF、GEF-H1、p190RhoGEF 和 AKAP-13 的同源物。Cysts 的缺失会导致一种表型，与顶端极性调节剂 Crumbs 的突变表型非常相似。这种表型可以被基底外侧极性蛋白的缺失所抑制，这表明 Cysts 是顶端极性蛋白网络的一个组成部分。我们证明 Cysts 通过与 Crumbs 复合物和 Bazooka/Par3 的相互作用被募集到顶侧膜。Cysts 在黏着连接激活 Rho1 并稳定连接肌球蛋白。在 Cysts 和 Crumbs 缺陷胚胎中，黏着连接肌球蛋白的耗竭是相似的。总之，我们的研究结果表明，Cysts 是 Crumbs 复合物的下游效应物，将顶端极性蛋白与黏着连接处的 Rho1 和肌球蛋白激活联系起来，支持连接的完整性和上皮极性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/ca47054449a7/JCB_201807106_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/23b178d7bc34/JCB_201807106_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/d0834ea7b772/JCB_201807106_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/f2188efa634e/JCB_201807106_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/313db1d962da/JCB_201807106_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/6ed03e229c8b/JCB_201807106_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/97df7a4b8ecd/JCB_201807106_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/ecc8088fd4d1/JCB_201807106_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/f94da251a028/JCB_201807106_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/5134a91ddd93/JCB_201807106_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/ca47054449a7/JCB_201807106_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/23b178d7bc34/JCB_201807106_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/d0834ea7b772/JCB_201807106_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/f2188efa634e/JCB_201807106_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/313db1d962da/JCB_201807106_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/6ed03e229c8b/JCB_201807106_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/97df7a4b8ecd/JCB_201807106_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/ecc8088fd4d1/JCB_201807106_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/f94da251a028/JCB_201807106_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/5134a91ddd93/JCB_201807106_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2be7/6781438/ca47054449a7/JCB_201807106_Fig10.jpg

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