Isoforms of the polarity protein par6 have distinct functions.
PAR-6 is essential for asymmetric division of the Caenorhabditis elegans zygote. It is also critical for cell polarization in many other contexts throughout the Metazoa. The Par6 protein contains a PDZ domain and a partial CRIB (Cdc42/Rac interactive binding) domain, which mediate interactions with other polarity proteins such as Par3, Cdc42, Pals1, and Lgl. A family of mammalian Par6 isoforms (Par6A-D) has been described, but the significance of this diversification has been unclear. Here we demonstrate that Par6 family members localize differently when expressed in Madin-Darby canine kidney epithelial cells and have distinct effects on tight junction (TJ) assembly. Par6B localizes to the cytosol and inhibits TJ formation, but Par6A co-localizes predominantly with the TJ marker ZO-1 at cell-cell contacts and does not affect junctions. These functional differences correlate with differences in Pals1 binding; Par6B interacts strongly with Pals1, whereas Par6A binds weakly to Pals1 even in the presence of active Cdc42. Pals1 has a low affinity for the isolated CRIB-PDZ domain of Par6A, but analysis of chimeras showed that in addition Pals1 binding is blocked by an inhibitory property of the N terminus of Par6A. Unexpectedly, the localization of Par6A to cell-cell contacts is Cdc42-independent.
Center for Cell Signaling, University of Virginia School of Medicine, Charlottesville, Virginia 22908-0577, USA.
Lin
L
Gao
Ian G
IG
Macara
D000595:Amino Acid Sequence; D000818:Animals; D029742:Caenorhabditis elegans Proteins; D002450:Cell Communication; D002460:Cell Line; D004847:Epithelial Cells / Q000166:cytology; D051528:Guanylate Kinases; D008322:Mammals; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology; D011506:Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D019108:Tight Junctions / Q000737:chemistry; D014162:Transfection
D029742:Caenorhabditis elegans Proteins; D020033:Protein Isoforms; D011506:Proteins; C512642:par-6 protein, C elegans; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases