Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial c

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. By performing a screen for genes that regulate epithelial architecture, Martín–Belmonte and colleagues identify key roles for the synaptotagmin-like proteins Slp2-a and Slp4-a in restricting lumen generation. They find that Slp2-a targets Rab27a/b-positive vesicles to PtdIns(4,5)P2-enriched apical membranes, whereas Slp4-a controls subsequent vesicle tethering and fusion. Their coordinated activities ensure the creation of a single lumen per cell.

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Gálvez-Santisteban, M., Rodriguez-Fraticelli, A., Bryant, D. et al. Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells. Nat Cell Biol 14, 838–849 (2012). https://doi.org/10.1038/ncb2541

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