Drosophila melanogaster Tango1 is required for secretion of Collagen IV. Liu et al. use a genetic analysis to show that Tango1 is required to spatially maintain the size and integrity of ER exit site–Golgi units and that loss of Tango1 function impairs not only Collagen IV secretion but also general secretion.

Highlights d Golgi in Drosophila contains a pre-cis-Golgi region equivalent to vertebrate ERGIC d COPII and COPI proteins localize to the center and periphery of ER exit sites, respectively d FIB-SEM imaging shows existence of vesicles consistent with COPI and COPII regular-sized vesicles d In addition to vesicles, FIB-SEM reveals short pearled tubes connecting ERES and Golgi

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.

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In the secretory pathway, the transfer of cargo from the ER to the Golgi involves dozens of proteins that localize at specific regions of the ER called ER exit sites (ERES), where cargos are concentrated preceding vesicular transport to the Golgi. Despite many years of research, we are missing crucial details of how this highly dynamic ER-Golgi interface is defined, maintained and functions. Mechanisms allowing secretion of large cargos such as the very abundant collagens are also poorly understood. In this context, Tango1, discovered in the fruit fly Drosophila and widely conserved in animal evolution, has received a lot of attention in recent years. Tango1, an ERES-localized transmembrane protein, is the single fly member of the MIA/cTAGE family, consisting in humans of TANGO1 and at least 14 different related proteins. After its discovery in flies, a specific role of human TANGO1 in mediating secretion of collagens was reported. However, multiple studies in Drosophila have demonstrated that Tango1 is required for secretion of all cargos. At all ERES, through self-interaction and interactions with other proteins, Tango1 aids ERES maintenance and tethering of post-ER membranes. In this review, we discuss discoveries on Drosophila Tango1 and put them in relation with research on human MIA/cTAGE proteins. In doing so, we aim to offer an integrated view of Tango1 function and the nature of ER-Golgi transport from an evolutionary perspective.