School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK.
School of Biosciences, University of Sheffield, Sheffield S10 2TN, UK.
Cell Rep. 2024 Oct 22;43(10):114722. doi: 10.1016/j.celrep.2024.114722. Epub 2024 Sep 19.
Fat and Dachsous are evolutionarily conserved atypical cadherins that regulate polarized cell behaviors. In the Drosophila wing, they interact heterophilically between neighboring cells, localize asymmetrically to opposite cell ends, and control wing shape by regulating oriented cell rearrangements and divisions. Fat and Dachsous have 34 and 27 cadherin repeats, respectively, and previous work has identified trans interactions between their first four cadherin repeats. Here, we identify a second heterophilic binding site in their C-terminal cadherin repeats and show the conservation of this binding site in human Fat4 and Dachsous1. We provide evidence that both N- and C-terminal binding sites regulate the stability of Fat-Dachsous binding interactions and show that the N-terminal binding sites are partly dispensable for Fat-Dachsous function in vivo. Finally, we provide in vivo confirmation that the N-terminal repeats interact in an anti-parallel manner. We propose that multiple binding sites promote the clustering of Fat and Dachsous into a lattice-like array.
脂肪（Fat）和 Dachsous 是进化上保守的非典型钙黏蛋白，它们调节极化细胞行为。在果蝇翅膀中，它们在相邻细胞之间异源相互作用，不对称地定位于细胞的相对两端，并通过调节定向细胞重排和分裂来控制翅膀形状。脂肪和 Dachsous 分别具有 34 个和 27 个钙黏蛋白重复序列，之前的工作已经确定了它们前四个钙黏蛋白重复序列之间的转相互作用。在这里，我们在它们的 C 端钙黏蛋白重复序列中鉴定出第二个异源结合位点，并显示该结合位点在人类 Fat4 和 Dachsous1 中的保守性。我们提供的证据表明，N 端和 C 端结合位点都调节 Fat-Dachsous 结合相互作用的稳定性，并且表明 N 端结合位点对于 Fat-Dachsous 在体内的功能不是必需的。最后，我们提供了体内确认，即 N 端重复序列以反平行的方式相互作用。我们提出，多个结合位点促进了 Fat 和 Dachsous 聚类成晶格状排列。
