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PMID: 14981097 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of cell biology ·Vol. 164 ·No. 5 ·2004-03-01 ·Pages 717-27

Cohen D, Brennwald PJ, Rodriguez-Boulan E, Müsch A

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.

MeSH Terms
Animals Caenorhabditis elegans Proteins/genetics,metabolism Cell Differentiation/physiology Cell Line Cell Polarity Cell Size Cytoskeleton/metabolism Dogs Epithelial Cells/cytology,physiology Gene Expression Regulation Humans Kidney/cytology Membrane Proteins/metabolism Microtubules/metabolism Morphogenesis/physiology Protein Serine-Threonine Kinases/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Tight Junctions/metabolism
Chemicals
Caenorhabditis elegans Proteins Membrane Proteins Recombinant Fusion Proteins EMK1 protein, Canis familiaris PAR-1 protein, C elegans Protein Serine-Threonine Kinases
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Cohen David
Margaret M. Dyson Vision Research Institute, Weill Medical College of Cornell University, 1300 York Ave., Box 233, New York, NY 10021, USA.
Brennwald Patrick J
Rodriguez-Boulan Enrique
Müsch Anne
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Article Info
Journal
The Journal of cell biology
Abbr.
J Cell Biol
ISSN
0021-9525
DOI
10.1083/jcb.200308104
Published
2004-03-01
Epub
2004-00-23
Pages
717-27
Language
English
Region
United States
NLM ID
0375356
PMCID
PMC2172160
Subset
IM
Grants
NIGMS NIH HHS · R01 GM034107 · United States
NIGMS NIH HHS · R01 GM054712 · United States
NIGMS NIH HHS · GM-34107 · United States
NIGMS NIH HHS · GM-54712 · United States
External Links
PubMed source DOI: 10.1083/jcb.200308104 PMC Full Text View journal details
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