Oligomerization of the FERM-FA protein Yurt controls epithelial cell polarity
Oligomerization of the FERM-FA protein Yurt controls epithelial cell polarity
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DOI：
10.1083/jcb.201803099
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发表时间：
2018-11-01
影响因子：
7.8
通讯作者：
Laprise, Patrick
中科院分区：
文献类型：
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作者：
Gamblin, Clemence L.;Parent-Prevost, Frederique;Laprise, Patrick
黑腹果蝇Yurt（Yrt）及其哺乳动物直向同源基因EPB 41 L5限制极化上皮细胞的顶膜生长。EPB 41 L5还支持上皮-间充质转化和转移。Yrt和EPB 41 L5含有四点一、埃兹蛋白、根蛋白和膜突蛋白（FERM）结构域和FERM邻近（FA）结构域。前者对50种人类蛋白质的四级结构有贡献，而后者定义了14种人类FERM蛋白质的亚家族，并履行未知的角色。在这项研究中，我们表明，Yrt和EPB 41 L5寡聚化。我们的数据还确定，FERM FA单元形成一个低聚物界面，Yrt的多聚化是至关重要的上皮细胞极性调节功能。最后，我们证明了aPKC使Yrt寡聚体不稳定以抑制其功能，从而揭示了这种激酶支持顶端结构域形成的机制。总体而言，我们的研究突出了苍蝇和人类Yrt蛋白的保守的生化特性，描述了FA结构域的新功能，并进一步表征了维持上皮细胞极性的分子机制。
Drosophila melanogaster Yurt (Yrt) and its mammalian orthologue EPB41L5 limit apical membrane growth in polarized epithelia. EPB41L5 also supports epithelial-mesenchymal transition and metastasis. Yrt and EPB41L5 contain a four-point-one, ezrin, radixin, and moesin (FERM) domain and a FERM-adjacent (FA) domain. The former contributes to the quaternary structure of 50 human proteins, whereas the latter defines a subfamily of 14 human FERM proteins and fulfills unknown roles. In this study, we show that both Yrt and EPB41L5 oligomerize. Our data also establish that the FERM-FA unit forms an oligomeric interface and that multimerization of Yrt is crucial for its function in epithelial cell polarity regulation. Finally, we demonstrate that aPKC destabilizes the Yrt oligomer to repress its functions, thereby revealing a mechanism through which this kinase supports apical domain formation. Overall, our study highlights a conserved biochemical property of fly and human Yrt proteins, describes a novel function of the FA domain, and further characterizes the molecular mechanisms sustaining epithelial cell polarity.