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

2012; Nature Portfolio; Volume: 14; Issue: 8 Linguagem: Inglês

10.1038/ncb2541

1476-4679

Manuel Gálvez-Santisteban, Alejo Rodriguez-Fraticelli, David M. Bryant, Silvia Vergarajauregui, Takao Yasuda, Inmaculada Bañón‐Rodríguez, Ilenia Bernascone, Anirban Datta, Natalie Spivak, Kitty Young, Christiaan L. Slim, Paul Brakeman, Mitsunori Fukuda, Keith E. Mostov, Fernando Martín‐Belmonte,

Erythrocyte Function and Pathophysiology

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.