title: Control of apico-basal epithelial polarity by the microtubule minus-end-binding protein CAMSAP3 and spectraplakin ACF7.
abstract: The microtubule cytoskeleton regulates cell polarity by spatially organizing membrane trafficking and signaling processes. In epithelial cells, microtubules form parallel arrays aligned along the apico-basal axis, and recent work has demonstrated that the members of CAMSAP/Patronin family control apical tethering of microtubule minus ends. Here, we show that in mammalian intestinal epithelial cells, the spectraplakin ACF7 (also known as MACF1) specifically binds to CAMSAP3 and is required for the apical localization of CAMSAP3-decorated microtubule minus ends. Loss of ACF7 but not of CAMSAP3 or its homolog CAMSAP2 affected the formation of polarized epithelial cysts in three-dimensional cultures. In short-term epithelial polarization assays, knockout of CAMSAP3, but not of CAMSAP2, caused microtubule re-organization into a more radial centrosomal array, redistribution of Rab11-positive (also known as Rab11A) endosomes from the apical cell surface to the pericentrosomal region and inhibition of actin brush border formation at the apical side of the cell. We conclude that ACF7 is an important regulator of apico-basal polarity in mammalian intestinal cells and that a radial centrosome-centered microtubule organization can act as an inhibitor of epithelial polarity.
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, The Netherlands.
authors: Ivar
authors: I
authors: Noordstra
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, The Netherlands.
authors: Qingyang
authors: Q
authors: Liu
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, The Netherlands.
authors: Wilco
authors: W
authors: Nijenhuis
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, The Netherlands.
authors: Shasha
authors: S
authors: Hua
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, The Netherlands.
authors: Kai
authors: K
authors: Jiang
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, The Netherlands.
authors: Matthijs
authors: M
authors: Baars
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, The Netherlands.
authors: Sanne
authors: S
authors: Remmelzwaal
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, The Netherlands.
authors: Maud
authors: M
authors: Martin
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, The Netherlands.
authors: Lukas C
authors: LC
authors: Kapitein
authors: Cell Biology, Department of Biology, Faculty of Science, Utrecht University, Padualaan 8, Utrecht 3584 CH, The Netherlands a.akhmanova@uu.nl.
authors: Anna
authors: 0000-0002-9048-8614
authors: A
authors: Akhmanova
mesh_terms: D018938:Caco-2 Cells; D016764:Cell Polarity; D004847:Epithelial Cells / Q000166:cytology* / Q000378:metabolism*; D055879:Gene Knock-In Techniques; D055785:Gene Knockdown Techniques; D049452:Green Fluorescent Proteins / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D008840:Microfilament Proteins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008871:Microvilli / Q000378:metabolism; D011485:Protein Binding
chemical_list: C000608274:Camsap3 protein, human; C095003:MACF1 protein, human; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D049452:Green Fluorescent Proteins
keywords: Apico–basal polarity; Brush border; Endosomes; Epithelial cells; Microtubule; Rab11