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)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.
ASJC Scopus subject areas
- Cell Biology