Inter-adipocyte Adhesion and Signaling by Collagen IV Intercellular Concentrations in Drosophila
Inter-adipocyte Adhesion and Signaling by Collagen IV Intercellular Concentrations in Drosophila
复制标题
果蝇中胶原 IV 细胞间浓度的脂肪细胞间粘附和信号传导
DOI：
10.1016/j.cub.2017.08.002
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发表时间：
2017-09-25
期刊：
影响因子：
9.2
通讯作者：
Pastor-Pareja, Jose C.
中科院分区：
文献类型：
--
作者：
Dai, Jianli;Ma, Mengqi;Pastor-Pareja, Jose C.
片状IV型胶原是基底膜的主要成分，基底膜是所有动物的上皮和周围器官下面的细胞外基质的平面聚合物。昆虫和哺乳动物的脂肪细胞都是起源于中胚层的，通常被归类为间充质细胞。然而，它们形成了真正的组织，在那里细胞保持紧密联系。提供这种组织水平组织的机制及其功能意义都不为人所知。在这里，我们表明，离散的IV型胶原细胞间浓度(CIFICS)，不同于基底膜，截面较厚，介导果蝇脂肪细胞间的黏附。幼虫脂肪体中这些含有IV型胶原的结构的丢失会导致细胞间隙和脂肪组织层的连续性中断。我们还发现，整合素和Syndecan基质受体将脂肪细胞附着在公民身上，并指导它们的形成。最后，我们证明了整合素介导的公民细胞黏附促进了正常脂肪细胞的生长，并通过Src-PI3K-Akt信号来防止自噬。我们的结果表明，IV型胶原在非上皮性组织形态发生中发挥了令人惊讶的非基底膜作用，同时展示了这些结构的黏附和信号功能。
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 tissuelevel 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.