Journal
NATURE CELL BIOLOGY
Volume 18, Issue 7, Pages 727-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb3374
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Funding
- University of Zurich
- Swiss National Science Foundation (SNF) [31003A_141093_1]
- Kanton Zurich
- 'Cells-in-Motion' Cluster of Excellence [EXC 1003-CiM]
- University of Munster
- Swiss National Science Foundation (SNF) [31003A_141093] Funding Source: Swiss National Science Foundation (SNF)
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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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