title: Alix-mediated assembly of the actomyosin-tight junction polarity complex preserves epithelial polarity and epithelial barrier.
abstract: Maintenance of epithelial cell polarity and epithelial barrier relies on the spatial organization of the actin cytoskeleton and proper positioning/assembly of intercellular junctions. However, how these processes are regulated is poorly understood. Here we reveal a key role for the multifunctional protein Alix in both processes. In a knockout mouse model of Alix, we identified overt structural changes in the epithelium of the choroid plexus and in the ependyma, such as asymmetrical cell shape and size, misplacement and abnormal beating of cilia, blebbing of the microvilli. These defects culminate in excessive cell extrusion, enlargement of the lateral ventricles and hydrocephalus. Mechanistically, we find that by interacting with F-actin, the Par complex and ZO-1, Alix ensures the formation and maintenance of the apically restricted actomyosin-tight junction complex. We propose that in this capacity Alix plays a role in the establishment of apical-basal polarity and in the maintenance of the epithelial barrier.
authors.affiliation: Department of Genetics, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Campos
authors.affiliation: Department of Genetics, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Qiu
authors.affiliation: Department of Genetics, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Elida
authors.initials: E
authors.lastname: Gomero
authors.affiliation: Cellular Imaging Shared Resource, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Randall
authors.initials: R
authors.lastname: Wakefield
authors.affiliation: Cellular Imaging Shared Resource, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Linda
authors.initials: L
authors.lastname: Horner
authors.affiliation: Laboratory of Imaging Tissue Structure and Function, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, Poland.
authors.forename: Wojciech
authors.initials: W
authors.lastname: Brutkowski
authors.affiliation: Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Young-Goo
authors.identifier: 0000-0002-4008-294X
authors.initials: YG
authors.lastname: Han
authors.affiliation: Department of Developmental Neurobiology, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: David
authors.initials: D
authors.lastname: Solecki
authors.affiliation: Cellular Imaging Shared Resource, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Sharon
authors.initials: S
authors.lastname: Frase
authors.affiliation: Institute of Biomedicine and Molecular Immunology, National Research Council, 90146 Palermo, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Bongiovanni
authors.affiliation: Department of Genetics, St Jude Children's Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA.
authors.forename: Alessandra
authors.initials: A
authors.lastname: d'Azzo
mesh_terms: D000199:Actins / Q000378:metabolism; D000205:Actomyosin / Q000378:metabolism*; D000818:Animals; D001812:Blood-Brain Barrier; D002135:Calcium-Binding Proteins / Q000502:physiology*; D016764:Cell Polarity; D002831:Choroid Plexus / Q000378:metabolism* / Q000648:ultrastructure; D004805:Ependyma / Q000648:ultrastructure; D004847:Epithelial Cells / Q000648:ultrastructure; D006849:Hydrocephalus / Q000209:etiology; D051379:Mice; D018345:Mice, Knockout; D019108:Tight Junctions / Q000378:metabolism*; D062826:Zonula Occludens-1 Protein / Q000378:metabolism
chemical_list: D000199:Actins; D002135:Calcium-Binding Proteins; C492144:Pdcd6ip protein, mouse; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D000205:Actomyosin