Mammalian PAR-1 determines epithelial lumen polarity by organizing the microtubule cytoskeleton

David Cohen, Patrick J. Brennwald, Enrique Rodriguez-Boulan, Anne Muesch

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

Epithelial differentiation involves the generation of luminal surfaces and of a noncentrosomal microtubule (MT) network aligned along the polarity axis. Columnar epithelia (e.g., kidney, intestine, and Madin-Darby canine kidney [MDCK] cells) generate apical lumina and orient MT vertically, whereas liver epithelial cells (hepatocytes and WIFB9 cells) generate lumina at cell-cell contact sites (bile canaliculi) and orient MTs horizontally. We report that knockdown or inhibition of the mammalian orthologue of Caenorhabditis elegans Par-1 (EMK1 and MARK2) during polarization of cultured MDCK and WIFB9 cells prevented development of their characteristic lumen and nonradial MT networks. Conversely, EMK1 overexpression induced the appearance of intercellular lumina and horizontal MT arrays in MDCK cells, making EMK1 the first known candidate to regulate the developmental branching decision between hepatic and columnar epithelial cells. Our experiments suggest that EMK1 primarily promotes reorganization of the MT network, consistent with the MT-regulating role of this gene product in other systems, which in turn controls lumen formation and position.

Original languageEnglish (US)
Pages (from-to)717-727
Number of pages11
JournalJournal of Cell Biology
Volume164
Issue number5
DOIs
StatePublished - Mar 1 2004
Externally publishedYes

Fingerprint

Cytoskeleton
Microtubules
Madin Darby Canine Kidney Cells
Epithelial Cells
Bile Canaliculi
Liver
Caenorhabditis elegans
Intestines
Hepatocytes
Cultured Cells
Epithelium
Kidney
Genes

Keywords

  • Apical surface
  • EMK1
  • MARK2
  • MDCK
  • WIFB

ASJC Scopus subject areas

  • Cell Biology

Cite this

Mammalian PAR-1 determines epithelial lumen polarity by organizing the microtubule cytoskeleton. / Cohen, David; Brennwald, Patrick J.; Rodriguez-Boulan, Enrique; Muesch, Anne.

In: Journal of Cell Biology, Vol. 164, No. 5, 01.03.2004, p. 717-727.

Research output: Contribution to journalArticle

Cohen, David ; Brennwald, Patrick J. ; Rodriguez-Boulan, Enrique ; Muesch, Anne. / Mammalian PAR-1 determines epithelial lumen polarity by organizing the microtubule cytoskeleton. In: Journal of Cell Biology. 2004 ; Vol. 164, No. 5. pp. 717-727.
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