Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Sinai Health System, Toronto, ON M5G 1X5, Canada;
Zoological Institute, Christian-Albrechts University of Kiel, 24118, Kiel, Germany.
Proc Natl Acad Sci U S A. 2020 Aug 11;117(32):19310-19320. doi: 10.1073/pnas.1917570117. Epub 2020 Jul 29.
Fat, Fat-like, and Dachsous family cadherins are giant proteins that regulate planar cell polarity (PCP) and cell adhesion in bilaterians. Their evolutionary origin can be traced back to prebilaterian species, but their ancestral function(s) are unknown. We identified Fat-like and Dachsous cadherins in , a member of phylum Cnidaria a sister group of bilaterian. We found does not possess a true Fat homolog, but has homologs of Fat-like (HyFatl) and Dachsous (HyDs) that localize at the apical membrane of ectodermal epithelial cells and are planar polarized perpendicular to the oral-aboral axis of the animal. Using a knockdown approach we found that HyFatl is involved in local cell alignment and cell-cell adhesion, and that reduction of HyFatl leads to defects in tissue organization in the body column. Overexpression and knockdown experiments indicate that the intracellular domain (ICD) of HyFatl affects actin organization through proline-rich repeats. Thus, planar polarization of Fat-like and Dachsous cadherins has ancient, prebilaterian origins, and Fat-like cadherins have ancient roles in cell adhesion, spindle orientation, and tissue organization.
脂肪蛋白、类脂肪蛋白和 Dachsous 家族钙黏蛋白是调控两侧对称动物的平面细胞极性（PCP）和细胞黏附的巨型蛋白。它们的进化起源可以追溯到前两侧对称动物，但它们的祖先功能尚不清楚。我们在刺胞动物门（栉水母动物门是其姐妹群，属于原口动物）的一员中鉴定到了类脂肪蛋白和 Dachsous 钙黏蛋白。我们发现该动物没有真正的 Fat 同源物，但有类脂肪蛋白（HyFatl）和 Dachsous（HyDs）的同源物，它们定位于外胚层上皮细胞的顶膜，沿动物的口-肛轴呈平面极化。通过敲低实验，我们发现 HyFatl 参与局部细胞对齐和细胞间黏附，并且 HyFatl 的减少会导致体柱组织的缺陷。过表达和敲低实验表明，HyFatl 的细胞内结构域（ICD）通过富含脯氨酸的重复序列影响肌动蛋白组织。因此，类脂肪蛋白和 Dachsous 钙黏蛋白的平面极化具有古老的、前两侧对称的起源，而类脂肪蛋白钙黏蛋白在细胞黏附、纺锤体取向和组织组织中具有古老的作用。
