ZEN-4/MKLP1 is required to polarize the foregut epithelium.
BACKGROUND
Epithelial tubes are a key component of organs and are generated from cells with distinct apico-basolateral polarity. Here, we describe a novel function during tubulogenesis for ZEN-4, the Caenorhabditis elegans ortholog of mitotic kinesin-like protein 1 (MKLP1), and CYK-4, which contains a RhoGAP (GTPase-activating protein) domain. Previous studies revealed that these proteins comprise centralspindlin (a complex that functions during mitosis to bundle microtubules), construct the spindle midzone, and complete cytokinesis.


RESULTS
Our analyses demonstrate that ZEN-4/MKLP1 functions postmitotically to establish the foregut epithelium. Mutants that lack ZEN-4/MKLP1 express polarity markers but fail to target these proteins appropriately to the cell cortex. Affected proteins include PAR-3/Bazooka and PKC-3/atypical protein kinase C at the apical membrane domain, and HMR-1/cadherin and AJM-1 within C. elegans apical junctions (CeAJ). Microtubules and actin are disorganized in zen-4 mutants compared to the wild-type.


CONCLUSIONS
We suggest that ZEN-4/MKLP1 and CYK-4/RhoGAP regulate an early step in epithelial polarization that is required to establish the apical domain and CeAJ.
Portereiko
Michael F
MF
Huntsman Cancer Institute, University of Utah, 2000 Circle of Hope, Salt Lake City, UT 84112 USA.
Saam
Jennifer
J
Mango
Susan E
SE
D000818:Animals; D015820:Cadherins / Q000378:metabolism; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D016764:Cell Polarity / Q000502:physiology*; D017931:DNA Primers; D004064:Digestive System / Q000166:cytology; D004848:Epithelium; D020690:GTPase-Activating Proteins / Q000378:metabolism*; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D016547:Kinesins / Q000378:metabolism*; D008164:Luminescent Proteins; D008870:Microtubules / Q000502:physiology*; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011493:Protein Kinase C / Q000378:metabolism; D013696:Temperature; D014170:Transformation, Genetic
C441580:AJM-1 protein, C elegans; D015820:Cadherins; D029742:Caenorhabditis elegans Proteins; D017931:DNA Primers; D020690:GTPase-Activating Proteins; D008164:Luminescent Proteins; C114455:ZEN-4 protein, C elegans; C085379:rho GTPase-activating protein; D049452:Green Fluorescent Proteins; C115015:PKC-3 protein; D011493:Protein Kinase C; D016547:Kinesins