Par1b induces asymmetric inheritance of plasma membrane domains via LGN-dependent mitotic spindle orientation in proliferating hepatocytes

PLoS Biol. 2013 Dec;11(12):e1001739. doi: 10.1371/journal.pbio.1001739. Epub 2013 Dec 17.

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Membrane / physiology*
  • Cell Polarity / physiology*
  • Cell Proliferation
  • Hep G2 Cells / physiology
  • Hepatocytes / physiology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / physiology*
  • Metalloproteases / physiology*
  • Mitochondrial Proteins / physiology*
  • Spindle Apparatus / physiology*

Substances

  • GPSM2 protein, human
  • Intracellular Signaling Peptides and Proteins
  • Mitochondrial Proteins
  • Metalloproteases
  • PARL protein, human