title: Par1b induces asymmetric inheritance of plasma membrane domains via LGN-dependent mitotic spindle orientation in proliferating hepatocytes.
abstract: The development and maintenance of polarized epithelial tissue requires a tightly controlled orientation of mitotic cell division relative to the apical polarity axis. Hepatocytes display a unique polarized architecture. We demonstrate that mitotic hepatocytes asymmetrically segregate their apical plasma membrane domain to the nascent daughter cells. The non-polarized nascent daughter cell can form a de novo apical domain with its new neighbor. This asymmetric segregation of apical domains is facilitated by a geometrically distinct "apicolateral" subdomain of the lateral surface present in hepatocytes. The polarity protein partitioning-defective 1/microtubule-affinity regulating kinase 2 (Par1b/MARK2) translates this positional landmark to cortical polarity by promoting the apicolateral accumulation of Leu-Gly-Asn repeat-enriched protein (LGN) and the capture of nuclear mitotic apparatus protein (NuMA)-positive astral microtubules to orientate the mitotic spindle. Proliferating hepatocytes thus display an asymmetric inheritance of their apical domains via a mechanism that involves Par1b and LGN, which we postulate serves the unique tissue architecture of the developing liver parenchyma.
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Christiaan L
authors.initials: CL
authors.lastname: Slim
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Francisco
authors.initials: F
authors.lastname: Lázaro-Diéguez
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Marjolein
authors.initials: M
authors.lastname: Bijlard
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Mathilda J M
authors.initials: MJ
authors.lastname: Toussaint
authors.affiliation: Department of Pathobiology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
authors.forename: Alain
authors.initials: A
authors.lastname: de Bruin
authors.affiliation: Institute of Molecular Medicine and Genetics, Department of Neurology, Medical College of Georgia, Georgia Regents University, Augusta, Georgia, United States of America.
authors.forename: Quansheng
authors.initials: Q
authors.lastname: Du
authors.affiliation: Department of Developmental and Molecular Biology, Albert Einstein College of Medicine, Bronx, New York, United States of America.
authors.forename: Anne
authors.initials: A
authors.lastname: Müsch
authors.affiliation: Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
authors.forename: Sven C D
authors.initials: SC
authors.lastname: van Ijzendoorn
mesh_terms: D002462:Cell Membrane / Q000502:physiology*; D016764:Cell Polarity / Q000502:physiology*; D049109:Cell Proliferation; D056945:Hep G2 Cells / Q000502:physiology; D022781:Hepatocytes / Q000502:physiology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology*; D045726:Metalloproteases / Q000502:physiology*; D024101:Mitochondrial Proteins / Q000502:physiology*; D008941:Spindle Apparatus / Q000502:physiology*
chemical_list: C102754:GPSM2 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D024101:Mitochondrial Proteins; D045726:Metalloproteases; C485223:PARL protein, human