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STRIPAK 调控 Slik 的定位以控制有丝分裂形态发生和上皮完整性。

STRIPAK regulates Slik localization to control mitotic morphogenesis and epithelial integrity.

机构信息

Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, Quebec, Canada.

Programmes de biologie moléculaire, Université de Montréal, Montréal, Quebec, Canada.

出版信息

J Cell Biol. 2020 Nov 2;219(11). doi: 10.1083/jcb.201911035.

DOI:10.1083/jcb.201911035
PMID:32960945
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7594492/
Abstract

Proteins of the ezrin, radixin, and moesin (ERM) family control cell and tissue morphogenesis. We previously reported that moesin, the only ERM in Drosophila, controls mitotic morphogenesis and epithelial integrity. We also found that the Pp1-87B phosphatase dephosphorylates moesin, counteracting its activation by the Ste20-like kinase Slik. To understand how this signaling pathway is itself regulated, we conducted a genome-wide RNAi screen, looking for new regulators of moesin activity. We identified that Slik is a new member of the striatin-interacting phosphatase and kinase complex (STRIPAK). We discovered that the phosphatase activity of STRIPAK reduces Slik phosphorylation to promote its cortical association and proper activation of moesin. Consistent with this finding, inhibition of STRIPAK phosphatase activity causes cell morphology defects in mitosis and impairs epithelial tissue integrity. Our results implicate the Slik-STRIPAK complex in the control of multiple morphogenetic processes.

摘要

埃兹蛋白、radixin 和 moesin (ERM) 家族的蛋白控制着细胞和组织形态发生。我们之前报道过，moesin 是果蝇中唯一的 ERM，它控制有丝分裂形态发生和上皮完整性。我们还发现，Pp1-87B 磷酸酶去磷酸化 moesin，抵消了它被 Ste20 样激酶 Slik 的激活。为了了解这个信号通路本身是如何被调控的，我们进行了全基因组 RNAi 筛选，寻找 moesin 活性的新调节因子。我们鉴定出 Slik 是 striatin 相互作用的磷酸酶和激酶复合物（STRIPAK）的一个新成员。我们发现 STRIPAK 的磷酸酶活性降低了 Slik 的磷酸化，从而促进了它在皮质的结合和 moesin 的正确激活。这一发现与以下结果一致，即抑制 STRIPAK 磷酸酶活性会导致有丝分裂中的细胞形态缺陷，并损害上皮组织的完整性。我们的研究结果表明，Slik-STRIPAK 复合物参与了多种形态发生过程的调控。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/3f0b599d34d9/JCB_201911035_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/5a1e0e35170c/JCB_201911035_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/07fbc3f57752/JCB_201911035_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/20516b9578b7/JCB_201911035_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/7ac7f39809b6/JCB_201911035_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/15469bcde8c7/JCB_201911035_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/a21dcbc897a8/JCB_201911035_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/03dc357e1ce8/JCB_201911035_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/ae77c9f71715/JCB_201911035_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/318f35a9a77d/JCB_201911035_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/db7fa39e42ce/JCB_201911035_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/574b84536206/JCB_201911035_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/e6c09949f4ef/JCB_201911035_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/ec8ad25bd302/JCB_201911035_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/3f0b599d34d9/JCB_201911035_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/5a1e0e35170c/JCB_201911035_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/07fbc3f57752/JCB_201911035_FigS1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/20516b9578b7/JCB_201911035_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/7ac7f39809b6/JCB_201911035_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/15469bcde8c7/JCB_201911035_FigS2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/a21dcbc897a8/JCB_201911035_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/03dc357e1ce8/JCB_201911035_FigS3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/ae77c9f71715/JCB_201911035_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/318f35a9a77d/JCB_201911035_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/db7fa39e42ce/JCB_201911035_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/574b84536206/JCB_201911035_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/e6c09949f4ef/JCB_201911035_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/ec8ad25bd302/JCB_201911035_FigS4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8bf4/7594492/3f0b599d34d9/JCB_201911035_Fig10.jpg

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