title: Tuba and N-WASP function cooperatively to position the central lumen during epithelial cyst morphogenesis.
abstract: The process of epithelial lumenogenesis requires coordination of a network of signaling machinery communicated to each cell through subsequent cell divisions. Formation of a single hollow lumen has previously been shown to require Tuba, a Cdc42 GEF, for Cdc42 activation and correct spindle orientation. Using a Caco-2 model of lumenogenesis, we show that knockdown (KD) of the actin regulator N-WASP, causes a multilumen phenotype similar to Tuba KD. Defects in lumenogenesis in Tuba KD and N-WASP KD cells are observed at the two cell stage with inappropriate marking of the pre-apical patch (PAP) - the precursor to lumen formation. Strikingly, both Tuba and N-WASP depend on each other for localization to the PAP. We conclude that N-WASP functions cooperatively with Tuba to facilitate lumenogenesis and this requires the polyproline region of N-WASP.
authors.affiliation: Division of Molecular Cell Biology, Institute for Molecular Bioscience, The University of Queensland-St. Lucia, QLD, Australia.
authors.forename: Eva M
authors.initials: EM
authors.lastname: Kovacs
authors.forename: Suzie
authors.initials: S
authors.lastname: Verma
authors.forename: Steven G
authors.initials: SG
authors.lastname: Thomas
authors.forename: Alpha S
authors.initials: AS
authors.lastname: Yap
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D015703:Antigens, CD; D018938:Caco-2 Cells; D015820:Cadherins / Q000378:metabolism; D002455:Cell Division; D016764:Cell Polarity; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism*; D055785:Gene Knockdown Techniques; D006801:Humans; D016086:Lentivirus / Q000235:genetics; D009024:Morphogenesis; D010455:Peptides / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D008941:Spindle Apparatus / Q000378:metabolism; D014162:Transfection; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000378:metabolism*; D020764:cdc42 GTP-Binding Protein / Q000378:metabolism
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; C482331:DNMBP protein, human; D010455:Peptides; D034741:RNA, Small Interfering; C495771:WASL protein, human; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; C011083:polyproline; D020764:cdc42 GTP-Binding Protein