TY - JOUR
T1 - Mammalian PAR-1 determines epithelial lumen polarity by organizing the microtubule cytoskeleton
AU - Cohen, David
AU - Brennwald, Patrick J.
AU - Rodriguez-Boulan, Enrique
AU - Müsch, Anne
PY - 2004/3/1
Y1 - 2004/3/1
N2 - 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.
AB - 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.
KW - Apical surface
KW - EMK1
KW - MARK2
KW - MDCK
KW - WIFB
UR - http://www.scopus.com/inward/record.url?scp=1442358790&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1442358790&partnerID=8YFLogxK
U2 - 10.1083/jcb.200308104
DO - 10.1083/jcb.200308104
M3 - Article
C2 - 14981097
AN - SCOPUS:1442358790
SN - 0021-9525
VL - 164
SP - 717
EP - 727
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 5
ER -