Journal
NATURE CELL BIOLOGY
Volume 14, Issue 8, Pages 838-U148Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncb2541
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Funding
- Human Frontiers Science Program (HFSP-CDA) [00011/2009]
- Marie Curie [IRG-209382]
- MICINN [BFU2008-01916, BFU2011-22622]
- CONSOLIDER [CSD2009-00016]
- NIH [R01DK074398, R01AI25144, R01DK91530]
- March of Dimes Basil O'Connor Starter Research Award
- JAE fellowship, from CSIC
- FPI fellowship, from MICINN
- AECC fellowship
- Fundacion Ramon Areces
- Grants-in-Aid for Scientific Research [20113006] Funding Source: KAKEN
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The formation of epithelial tissues requires both the generation of apical-basal polarity and the coordination of this polarity between neighbouring cells to form a central lumen. During de novo lumen formation, vectorial membrane transport contributes to the formation of a singular apical membrane, resulting in the contribution of each cell to only a single lumen. Here, from a functional screen for genes required for three-dimensional epithelial architecture, we identify key roles for synaptotagmin-like proteins 2-a and 4-a (Slp2-a/4-a) in the generation of a single apical surface percell. Slp2-a localizes to the luminal membrane in a PtdIns(4,5)P-2-dependent manner, where it targets Rab27-loaded vesicles to initiate a single lumen. Vesicle tethering and fusion is controlled by Slp4-a, in conjunction with Rab27/Rab3/Rab8 and the SNARE syntaxin-3. Together, Slp2-a/4-a coordinate the spatiotemporal organization of vectorial apical transport to ensure that only a single apical surface, and thus the formation of a single lumen, occurs per cell.
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