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The matrix protein Collagen IV is widely considered an exclusive component of the thin, planar basement membranes supporting tissues in all animals. However, researchers from the Tissue Morphogenesis lab in Tsinghua School of Life Sciences have just discovered a novel type of Collagen IV-containing structure distinct from basement membranes. In their study of how the fat tissue of Drosophila fruit flies is organized, Jianli Dai and co-workers found that many discrete Collagen IV-containing concentrations exist between individual adipocytes. Experiments conducted by Jose Pastor-Pareja’s group further show that these Collagen IV intercellular concentrations (CIVICs) play both structural roles in tissue organization and signaling roles in adipocyte survival.
Sheet-forming Collagen IV is the main component of basement membranes: 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. Dai et al. 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. Integrin and Syndecan matrix receptors attach adipocytes to CIVICs and direct their formation. Finally, Integrin-mediated adhesion to CIVICs promotes normal adipocyte growth and prevents autophagy through Src-PI3K-Akt signaling. Results from the study evidence a surprising non-basement membrane role of Collagen IV in non-epithelial tissue morphogenesis while demonstrating adhesion and signaling functions for these structures.
The article, entitled “Inter-adipocyte Adhesion and Signaling by Collagen IV Intercellular Concentrations in Drosophila”, has been published online in Current Biology on August 31st, 2017. The work was conducted entirely in Jose C. Pastor-Pareja’s laboratory of the School of Life Sciences at Tsinghua University. Ph.D. student Jianli Dai (female, CLS program) is the first author of the work, to which Ph.D. students Mengqi Ma (female, PTN program) and Feng Zhi (male, Tsinghua) also contributed. The research was funded by the Natural Science Foundation of China, Tsinghua Initiative program and 1,000 Talents program.
Figure: Role of CIVICs (Collagen IV Intercellular Concentrations) in inter-adipocyte adhesion and signaling.
http://www.cell.com/current-biology/fulltext/S0960-9822(17)31011-4
http://joselab.www.niepad.com/
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