School of Life Sciences, Tsinghua University, Beijing 100084, China.
School of Life Sciences, Tsinghua University, Beijing 100084, China.
Curr Biol. 2017 Sep 25;27(18):2729-2740.e4. doi: 10.1016/j.cub.2017.08.002. Epub 2017 Aug 31.
Sheet-forming Collagen IV is the main component of basement membranes, which are planar polymers of extracellular matrix underlying epithelia and surrounding organs in all animals. Adipocytes in both insects and mammals are mesodermal in origin and often classified as mesenchymal. However, they form true tissues where cells remain compactly associated. Neither the mechanisms providing this tissue-level organization nor its functional significance are known. Here we show that discrete Collagen IV intercellular concentrations (CIVICs), distinct from basement membranes and thicker in section, mediate inter-adipocyte adhesion in Drosophila. Loss of these Collagen-IV-containing structures in the larval fat body caused intercellular gaps and disrupted continuity of the adipose tissue layer. We also found that Integrin and Syndecan matrix receptors attach adipocytes to CIVICs and direct their formation. Finally, we show that Integrin-mediated adhesion to CIVICs promotes normal adipocyte growth and prevents autophagy through Src-Pi3K-Akt signaling. Our results evidence a surprising non-basement membrane role of Collagen IV in non-epithelial tissue morphogenesis while demonstrating adhesion and signaling functions for these structures.
片状胶原蛋白 IV 是基底膜的主要成分，基底膜是所有动物上皮细胞和周围器官下方细胞外基质的平面聚合物。昆虫和哺乳动物中的脂肪细胞都起源于中胚层，通常被归类为间充质细胞。然而，它们形成了真正的组织，其中细胞仍然紧密相关。提供这种组织水平组织的机制及其功能意义尚不清楚。在这里，我们表明，在果蝇中，离散的细胞间胶原蛋白 IV 浓度（CIVICs）与基底膜不同，在切片中更厚，介导脂肪细胞间的黏附。幼虫脂肪体中这些含有胶原蛋白-IV 的结构的缺失导致细胞间间隙，并破坏脂肪组织层的连续性。我们还发现，整联蛋白和连接蛋白基质受体将脂肪细胞附着到 CIVICs 上，并指导其形成。最后，我们表明，整联蛋白与 CIVICs 的黏附通过 Src-Pi3K-Akt 信号促进脂肪细胞的正常生长并防止自噬。我们的结果证明了胶原蛋白 IV 在非上皮组织形态发生中的一个惊人的非基底膜作用，同时证明了这些结构的黏附和信号功能。
