Antagonistic functions of Par-1 kinase and protein phosphatase 2A are required for localization of Bazooka and photoreceptor morphogenesis in Drosophila.
Establishment and maintenance of apical basal cell polarity are essential for epithelial morphogenesis and have been studied extensively using the Drosophila eye as a model system. Bazooka (Baz), a component of the Par-6 complex, plays important roles in cell polarity in diverse cell types including the photoreceptor cells. In ovarian follicle cells, localization of Baz at the apical region is regulated by Par-1 protein kinase. In contrast, Baz in photoreceptor cells is targeted to adherens junctions (AJs). To examine the regulatory pathways responsible for Baz localization in photoreceptor cells, we studied the effects of Par-1 on Baz localization in the pupal retina. Loss of Par-1 impairs the maintenance of AJ markers including Baz and apical polarity proteins of photoreceptor cells but not the establishment of cell polarity. In contrast, overexpression of Par-1 or Baz causes severe mislocalization of junctional and apical markers, resulting in abnormal cell polarity. However, flies with similar overexpression of kinase-inactive mutant Par-1 or unphosphorylatable mutant Baz protein show relatively normal photoreceptor development. These results suggest that dephosphorylation of Baz at the Par-1 phosphorylation sites is essential for proper Baz localization. We also show that the inhibition of protein phosphatase 2A (PP2A) mimics the polarity defects caused by Par-1 overexpression. Furthermore, Par-1 gain-of-function phenotypes are strongly enhanced by reduced PP2A function. Thus, we propose that antagonism between PP2A and Par-1 plays a key role in Baz localization at AJ in photoreceptor morphogenesis.
Nam
Sang-Chul
SC
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
Mukhopadhyay
Bibhash
B
Choi
Kwang-Wook
KW
D000818:Animals; D004330:Drosophila / Q000235:genetics*; D029721:Drosophila Proteins / Q000235:genetics* / Q000502:physiology*; D004331:Drosophila melanogaster; D005260:Female; D018507:Gene Expression Regulation, Developmental; D038362:Glycogen Synthase Kinase 3; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000502:physiology*; D008297:Male; D008938:Mitosis; D008954:Models, Biological; D006080:Ovarian Follicle / Q000196:embryology*; D010749:Phosphoprotein Phosphatases / Q000235:genetics* / Q000502:physiology*; D010766:Phosphorylation; D017956:Photoreceptor Cells, Invertebrate / Q000196:embryology*; D011493:Protein Kinase C / Q000378:metabolism; D054648:Protein Phosphatase 2; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000502:physiology*
D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C400774:baz protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D011493:Protein Kinase C; D038362:Glycogen Synthase Kinase 3; C472496:Par-1 protein, Drosophila; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2