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黏着连接相关 LIM 结构域蛋白 Smallish 调控上皮形态发生。

The adherens junction-associated LIM domain protein Smallish regulates epithelial morphogenesis.

机构信息

Stem Cell Biology, Institute for Anatomy and Cell Biology, Georg-August-University Göttingen, Göttingen, Germany.

Developmental Genetics, Institute for Biology, University of Kassel, Kassel, Germany.

出版信息

J Cell Biol. 2018 Mar 5;217(3):1079-1095. doi: 10.1083/jcb.201610098. Epub 2018 Jan 22.

DOI:10.1083/jcb.201610098
PMID:29358210
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5839775/
Abstract

In epithelia, cells adhere to each other in a dynamic fashion, allowing the cells to change their shape and move along each other during morphogenesis. The regulation of adhesion occurs at the belt-shaped adherens junction, the zonula adherens (ZA). Formation of the ZA depends on components of the Par-atypical PKC (Par-aPKC) complex of polarity regulators. We have identified the Lin11, Isl-1, Mec-3 (LIM) protein Smallish (Smash), the orthologue of vertebrate LMO7, as a binding partner of Bazooka/Par-3 (Baz), a core component of the Par-aPKC complex. Smash also binds to Canoe/Afadin and the tyrosine kinase Src42A and localizes to the ZA in a planar polarized fashion. Animals lacking Smash show loss of planar cell polarity (PCP) in the embryonic epidermis and reduced cell bond tension, leading to severe defects during embryonic morphogenesis of epithelial tissues and organs. Overexpression of Smash causes apical constriction of epithelial cells. We propose that Smash is a key regulator of morphogenesis coordinating PCP and actomyosin contractility at the ZA.

摘要

在上皮组织中，细胞以动态方式相互黏附，使细胞能够在形态发生过程中改变形状并相互移动。黏附的调节发生在带状黏附连接，即黏附连接带（ZA）。ZA 的形成取决于极性调节剂 Par-typical PKC（Par-aPKC）复合物的成分。我们已经确定了 Lin11、Isl-1、Mec-3（LIM）蛋白 Smallish（Smash），即脊椎动物 LMO7 的同源物，作为 Bazooka/Par-3（Baz）的结合伴侣，Baz 是 Par-aPKC 复合物的核心成分。Smash 还与 Canoe/Afadin 和酪氨酸激酶 Src42A 结合，并以平面极化的方式定位到 ZA。缺乏 Smash 的动物在胚胎表皮中失去平面细胞极性（PCP），并且细胞黏附张力降低，导致上皮组织和器官在胚胎形态发生过程中出现严重缺陷。Smash 的过表达导致上皮细胞的顶端收缩。我们提出，Smash 是形态发生的关键调节剂，协调 ZA 处的 PCP 和肌动球蛋白收缩性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/55d39dafe542/JCB_201610098_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/2fa16b00126a/JCB_201610098_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/8b931315c0f0/JCB_201610098_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/89de03396a9e/JCB_201610098_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/34984b0b37d0/JCB_201610098_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/1d6b6024761c/JCB_201610098_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/9c2251be32cf/JCB_201610098_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/b265dd9e082e/JCB_201610098_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/242fbf0b7410/JCB_201610098_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/965b9a9a1d66/JCB_201610098_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/55d39dafe542/JCB_201610098_Fig10.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/2fa16b00126a/JCB_201610098_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/8b931315c0f0/JCB_201610098_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/89de03396a9e/JCB_201610098_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/34984b0b37d0/JCB_201610098_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/1d6b6024761c/JCB_201610098_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/9c2251be32cf/JCB_201610098_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/b265dd9e082e/JCB_201610098_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/242fbf0b7410/JCB_201610098_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/965b9a9a1d66/JCB_201610098_Fig9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dda9/5839775/55d39dafe542/JCB_201610098_Fig10.jpg

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