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          Institute: MPI für molekulare Zellbiologie und Genetik     Collection: MPI-CBG Publications 2016 (archival)     Display Documents



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ID: 732447.0, MPI für molekulare Zellbiologie und Genetik / MPI-CBG Publications 2016 (archival)
Staccato/Unc-13-4 controls secretory lysosome-mediated lumen fusion during epithelial tube anastomosis.
Authors:Caviglia, Sara; Brankatschk, Marko; Fischer, Elisabeth; Eaton, Suzanne; Luschnig, Stefan
Date of Publication (YYYY-MM-DD):2016
Title of Journal:Nature Cell Biology
Volume:18
Issue / Number:7
Start Page:727
End Page:739
Copyright:not available
Audience:Experts Only
Intended Educational Use:No
Abstract / Description: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.
External Publication Status:published
Document Type:Article
Version Comment:Automatic journal name synchronization
Communicated by:Thüm
Affiliations:MPI für molekulare Zellbiologie und Genetik
Identifiers:LOCALID:6589
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