Staccato/Unc-13-4 controls secretory lysosome-mediated lumen fusion during epithelial tube anastomosis

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Abstract

A crucial yet ill-defined step during the development of tubular networks, such as the vasculature, is the formation of connections (anastomoses) between pre-existing lumenized tubes. By studying tracheal tube anastomosis in Drosophila melanogaster, we uncovered a key role of secretory lysosome-related organelle (LRO) trafficking in lumen fusion. We identified the conserved calcium-binding protein Unc-13-4/Staccato (Stac) and the GTPase Rab39 as critical regulators of this process. Stac and Rab39 accumulate on dynamic vesicles, which form exclusively in fusion tip cells, move in a dynein-dependent manner, and contain late-endosomal, lysosomal, and SNARE components characteristic of LROs. The GTPase Arl3 is necessary and sufficient for Stac LRO formation and promotes Stac-dependent intracellular fusion of juxtaposed apical plasma membranes, thereby forming a transcellular lumen. Concomitantly, calcium is released locally from ER exit sites and apical membrane-associated calcium increases. We propose that calcium-dependent focused activation of LRO exocytosis restricts lumen fusion to appropriate domains within tip cells.

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Caviglia, S., Brankatschk, M., Fischer, E. J., Eaton, S., & Luschnig, S. (2016). Staccato/Unc-13-4 controls secretory lysosome-mediated lumen fusion during epithelial tube anastomosis. Nature Cell Biology, 18(7), 727–739. https://doi.org/10.1038/ncb3374

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