Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells
Open Access
- 22 July 2012
- journal article
- research article
- Published by Springer Science and Business Media LLC in Nature
- Vol. 14 (8), 838-849
- https://doi.org/10.1038/ncb2541
Abstract
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 per cell. Slp2-a localizes to the luminal membrane in a PtdIns(4,5)P2-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.Keywords
This publication has 37 references indexed in Scilit:
- Molecular Regulation of Lumen MorphogenesisCurrent Biology, 2011
- Rab GTPase–Myo5B complexes control membrane recycling and epithelial polarizationProceedings of the National Academy of Sciences of the United States of America, 2011
- A molecular network for de novo generation of the apical surface and lumenNature, 2010
- The Cdc42 GEF Intersectin 2 controls mitotic spindle orientation to form the lumen during epithelial morphogenesisThe Journal of cell biology, 2010
- From cells to organs: building polarized tissueNature Reviews Molecular Cell Biology, 2008
- Genetic control of single lumen formation in the zebrafish gutNature, 2007
- Loss of endocytic clathrin-coated pits upon acute depletion of phosphatidylinositol 4,5-bisphosphateProceedings of the National Academy of Sciences of the United States of America, 2007
- Exophilin4/Slp2-a Targets Glucagon Granules to the Plasma Membrane through Unique Ca2+-inhibitory Phospholipid-binding Activity of the C2A DomainMolecular Biology of the Cell, 2007
- PTEN-Mediated Apical Segregation of Phosphoinositides Controls Epithelial Morphogenesis through Cdc42Cell, 2007
- Phosphatidylinositol-3,4,5-trisphosphate regulates the formation of the basolateral plasma membrane in epithelial cellsNature, 2006