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.
Many chronic diseases are associated with fibrotic deposition of Collagen and other matrix proteins. Little is known about the factors that determine preferential onset of fibrosis in particular tissues. Here we show that plasma membrane (PM) overgrowth causes pericellular Collagen accumulation in Drosophila adipocytes. We found that loss of Dynamin and other endocytic components causes pericellular trapping of outgoing Collagen IV due to dramatic cortex expansion when endocytic removal of PM is prevented. Deposits also form in the absence of negative Toll immune regulator Cactus, excess PM being caused in this case by increased secretion. Finally, we show that trimeric Collagen accumulation, downstream of Toll or endocytic defects, activates a tissue damage response. Our work indicates that traffic imbalances and PM topology may contribute to fibrosis. It also places fibrotic deposits both downstream and upstream of immune signaling, consistent with the chronic character of fibrotic diseases.DOI:
http://dx.doi.org/10.7554/eLife.07187.001
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
Secretory cargos are collected at ER exit sites (ERES) before transport to the Golgi apparatus. Decades of research have provided many details of the molecular events underlying ER-Golgi exchanges. Essential questions, however, remain about the organization of the ER-Golgi interface in cells and the type of membrane structures mediating traffic from ERES. To investigate these, we used transgenic tagging in Drosophila flies, 3D-SIM and FIB-SEM to characterize ERES-Golgi units in collagen-producing fat body, imaginal discs and imaginal discs overexpressing ERES determinant Tango1. We found in front of ERES a pre-cis-Golgi region involved in both anterograde and retrograde transport. This pre-cis-Golgi is continuous with the rest of the Golgi, not a separate intermediate compartment or collection of large carriers, for which we found no evidence. We found, however, many vesicles, as well as pearled tubules connecting ERES and Golgi.
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