Hepatocyte polarity

Aleksandr Treyer, Anne Muesch

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Hepatocytes, like other epithelia, are situated at the interface between the organism's exterior and the underlying internal milieu and organize the vectorial exchange of macromolecules between these two spaces. To mediate this function, epithelial cells, including hepatocytes, are polarized with distinct luminal domains that are separated by tight junctions from lateral domains engaged in cell-cell adhesion and from basal domains that interact with the underlying extracellular matrix. Despite these universal principles, hepatocytes distinguish themselves from other nonstriated epithelia by their multipolar organization. Each hepatocyte participates in multiple, narrow lumina, the bile canaliculi, and has multiple basal surfaces that face the endothelial lining. Hepatocytes also differ in the mechanism of luminal protein trafficking from other epithelia studied. They lack polarized protein secretion to the luminal domain and target single-spanning and glycosylphosphatidylinositol-anchored bile canalicular membrane proteins via transcytosis from the basolateral domain. We compare this unique hepatic polarity phenotype with that of the more common columnar epithelial organization and review our current knowledge of the signaling mechanisms and the organization of polarized protein trafficking that govern the establishment and maintenance of hepatic polarity. The serine/threonine kinase LKB1, which is activated by the bile acid taurocholate and, in turn, activates adenosine monophosphate kinase-related kinases including AMPK1/2 and Par1 paralogues has emerged as a key determinant of hepatic polarity. We propose that the absence of a hepatocyte basal lamina and differences in cell-cell adhesion signaling that determine the positioning of tight junctions are two crucial determinants for the distinct hepatic and columnar polarity phenotypes.

Original languageEnglish (US)
Pages (from-to)243-287
Number of pages45
JournalComprehensive Physiology
Volume3
Issue number1
DOIs
StatePublished - 2013

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Hepatocytes
Epithelium
Tight Junctions
Liver
Protein Transport
Cell Adhesion
Adenosine Kinase
Bile Canaliculi
Phenotype
Transcytosis
Glycosylphosphatidylinositols
Taurocholic Acid
Protein-Serine-Threonine Kinases
Adenosine Monophosphate
Bile Acids and Salts
Basement Membrane
Bile
Extracellular Matrix
Membrane Proteins
Phosphotransferases

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Hepatocyte polarity. / Treyer, Aleksandr; Muesch, Anne.

In: Comprehensive Physiology, Vol. 3, No. 1, 2013, p. 243-287.

Research output: Contribution to journalArticle

Treyer, Aleksandr ; Muesch, Anne. / Hepatocyte polarity. In: Comprehensive Physiology. 2013 ; Vol. 3, No. 1. pp. 243-287.
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