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Nat Cell Biol. 2016 Jul;18(7):727-39. doi: 10.1038/ncb3374. Epub 2016 Jun 20.

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

Author information

1
Institute of Molecular Life Sciences and Ph.D. Program in Molecular Life Sciences, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
2
Max-Planck Institute of Molecular Cell Biology and Genetics, Pfotenhauerstrasse 108, D-01307 Dresden, Germany.
3
Institute of Neurobiology, University of Münster, Badestrasse 9, D-48149 Münster, Germany.
4
Cells-in-Motion Cluster of Excellence (EXC 1003 - CiM), University of Münster, D-48149 Münster, Germany.

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.

PMID:
27323327
DOI:
10.1038/ncb3374
[Indexed for MEDLINE]

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