title: Synaptotagmin-like proteins control the formation of a single apical membrane domain in epithelial cells.
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)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.
authors: Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, C/Nicolás Cabrera 1, Madrid 28049, Spain.
authors: Manuel
authors: M
authors: Gálvez-Santisteban
authors: Alejo E
authors: AE
authors: Rodriguez-Fraticelli
authors: David M
authors: DM
authors: Bryant
authors: Silvia
authors: S
authors: Vergarajauregui
authors: Takao
authors: T
authors: Yasuda
authors: Inmaculada
authors: I
authors: Bañón-Rodríguez
authors: Ilenia
authors: I
authors: Bernascone
authors: Anirban
authors: A
authors: Datta
authors: Natalie
authors: N
authors: Spivak
authors: Kitty
authors: K
authors: Young
authors: Christiaan L
authors: CL
authors: Slim
authors: Paul R
authors: PR
authors: Brakeman
authors: Mitsunori
authors: M
authors: Fukuda
authors: Keith E
authors: KE
authors: Mostov
authors: Fernando
authors: F
authors: Martín-Belmonte
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism*; D016764:Cell Polarity; D004847:Epithelial Cells / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006801:Humans; D046228:Microarray Analysis; D018613:Microscopy, Confocal; D016133:Polymerase Chain Reaction; D050857:Synaptotagmins / Q000378:metabolism*
chemical_list: D050857:Synaptotagmins