PAR-6, but not E-cadherin and β-integrin, is necessary for epithelial polarization in C. elegans.
PAR-6, but not E-cadherin and β-integrin, is necessary for epithelial polarization in C. elegans.
复制标题
PAR-6，但不是E-钙粘蛋白和β-整合素，是线虫上皮极化所必需的。
DOI：
10.1016/j.ydbio.2015.03.002
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发表时间：
2015
影响因子：
2.7
通讯作者：
Mango,SusanE
中科院分区：
文献类型：
--
作者：
VonStetina,StephenE;Mango,SusanE
细胞极性是上皮细胞的基本特征。经典的细胞生物学研究表明，极化上皮的建立和取向取决于由外向内的线索，这些线索来源于与相邻细胞或基质的相互作用（Akhtar和Streuli，2013; Chen和Zhang，2013; Chung和Andrew，2008;麦克尼尔等人，1990; Nejsum和纳尔逊，2007;纳尔逊等人，2013年; Ojakian和Schwimmer，1994年; Wang等人，1990; Yu等人，2005年）。这种范例已经受到在不存在介导细胞-细胞或细胞-基质相互作用的分子，特别是E-钙粘蛋白和整联蛋白的情况下产生的上皮细胞的实例的挑战（Baas等人，2004; Choi等人，2013; Costa等人，1998; Harris和Peifer，2004; Raich等人，1999; Roote和Zusman，1995; Vestweber等人，1985;威廉姆斯和Waterston，1994; Wu等人，2009年）。在这里，我们探索了另一种假设，即钙粘蛋白和整联蛋白在上皮形成过程中冗余地起作用以彼此替代（Martinez-Rico et al.，2010; Ojakian等人，2001; Rudkouskaya等人，2014; Weber等人，2011年）。我们使用C。elegans，它拥有单个E-钙粘蛋白（Costa等人，1998;哈丁等人，2013; Tepass，1999）和单一β-整联蛋白（Gettner et al.，1995; Lee等人，2001），并分析拱廊细胞，其在胚胎发生后期产生上皮（Portereiko和Mango，2001; Portereiko等人，2004年，在大多数产妇因素耗尽后。E-钙粘蛋白（HMR-1）和β-整联蛋白（PAT-3）的缺失对拱状细胞上皮、表皮或消化道的发生或形成没有影响。此外，β-整联蛋白（PAT-3）在拱廊的基底表面不富集，并且直到拱廊细胞极性建立之后才检测到候选PAT-3结合配偶体β-层粘连蛋白（LAM-1），并且当突变时没有表现出明显的极性缺陷。相反，极性蛋白par-6（Chen和Zhang，2013; Watts等人，1996），并且par-6突变体表现出错误定位或缺乏顶端和连接蛋白。我们的结论是，拱状细胞上皮极化的PAR-6介导的途径是独立的E-钙粘蛋白，β-整合素和β-层粘连蛋白。
Cell polarity is a fundamental characteristic of epithelial cells. Classical cell biological studies have suggested that establishment and orientation of polarized epithelia depend on outside-in cues that derive from interactions with either neighboring cells or the substratum (Akhtar and Streuli, 2013; Chen and Zhang, 2013; Chung and Andrew, 2008; McNeill et al., 1990; Nejsum and Nelson, 2007; Nelson et al., 2013; Ojakian and Schwimmer, 1994; Wang et al., 1990; Yu et al., 2005). This paradigm has been challenged by examples of epithelia generated in the absence of molecules that mediate cell-cell or cell-matrix interactions, notably E-cadherin and integrins (Baas et al., 2004; Choi et al., 2013; Costa et al., 1998; Harris and Peifer, 2004; Raich et al., 1999; Roote and Zusman, 1995; Vestweber et al., 1985; Williams and Waterston, 1994; Wu et al., 2009). Here we explore an alternative hypothesis, that cadherins and integrins function redundantly to substitute for one another during epithelium formation (Martinez-Rico et al., 2010; Ojakian et al., 2001; Rudkouskaya et al., 2014; Weber et al., 2011). We use C. elegans, which possesses a single E-cadherin (Costa et al., 1998; Hardin et al., 2013; Tepass, 1999) and a single β-integrin (Gettner et al., 1995; Lee et al., 2001), and analyze the arcade cells, which generate an epithelium late in embryogenesis (Portereiko and Mango, 2001; Portereiko et al., 2004), after most maternal factors are depleted. Loss of E-cadherin (HMR-1) in combination with β-integrin (PAT-3) had no impact on the onset or formation of the arcade cell epithelium, nor the epidermis or digestive tract. Moreover, ß-integrin (PAT-3) was not enriched at the basal surface of the arcades, and the candidate PAT-3 binding partner β-laminin (LAM-1) was not detected until after arcade cell polarity was established and exhibited no obvious polarity defect when mutated. Instead, the polarity protein par-6 (Chen and Zhang, 2013; Watts et al., 1996) was required to polarize the arcade cells, and par-6 mutants exhibited mislocalized or absent apical and junctional proteins. We conclude that the arcade cell epithelium polarizes by a PAR-6-mediated pathway that is independent of E-cadherin, β-integrin and β-laminin.