Staccato/Unc-13-4 controls secretory lysosome-mediated lumen fusion during epithelial tube anastomosis
Research output: Contribution to journal › Research article › Contributed › peer-review
Contributors
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.
Details
Original language | English |
---|---|
Pages (from-to) | 727-739 |
Number of pages | 13 |
Journal | Nature cell biology |
Volume | 18 |
Issue number | 7 |
Publication status | Published - 28 Jun 2016 |
Peer-reviewed | Yes |
External IDs
PubMed | 27323327 |
---|