PP2A antagonizes phosphorylation of Bazooka by PAR-1 to control apical-basal polarity in dividing embryonic neuroblasts.
Bazooka/Par-3 (Baz) is a key regulator of cell polarity in epithelial cells and neuroblasts (NBs). Phosphorylation of Baz by PAR-1 and aPKC is required for its function in epithelia, but little is known about the dephosphorylation mechanisms that antagonize the activities of these kinases or about the relevance of Baz phosphorylation for NB polarity. We found that protein phosphatase 2A (PP2A) binds to Baz via its structural A subunit. By using phospho-specific antibodies, we show that PP2A dephosphorylates Baz at the conserved serine residue 1085 and thereby antagonizes the kinase activity of PAR-1. Loss of PP2A function leads to complete reversal of polarity in NBs, giving rise to an "upside-down" polarity phenotype. Overexpression of PAR-1 or Baz, or mutation of 14-3-3 proteins that bind phosphorylated Baz, causes essentially the same phenotype, indicating that the balance of PAR-1 and PP2A effects on Baz phosphorylation determines NB polarity.
Krahn
Michael P
MP
Abteilung Stammzellbiologie, DFG Research Center for Molecular Physiology of the Brain, Georg-August-Universität Göttingen, Göttingen, Germany.
Egger-Adam
Diane
D
Wodarz
Andreas
A
D048948:14-3-3 Proteins / Q000378:metabolism; D000818:Animals; D045163:Antibodies, Phospho-Specific / Q000378:metabolism; D002455:Cell Division; D002460:Cell Line; D016764:Cell Polarity; D017124:Conserved Sequence; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology* / Q000201:enzymology; D004625:Embryo, Nonmammalian / Q000166:cytology* / Q000201:enzymology; D038362:Glycogen Synthase Kinase 3; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008677:Metaphase; D009154:Mutation / Q000235:genetics; D009474:Neurons / Q000166:cytology / Q000201:enzymology*; D010641:Phenotype; D010766:Phosphorylation; D010768:Phosphoserine / Q000378:metabolism; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism; D054648:Protein Phosphatase 2 / Q000037:antagonists & inhibitors / Q000172:deficiency / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*
D048948:14-3-3 Proteins; D045163:Antibodies, Phospho-Specific; D029721:Drosophila Proteins; D047908:Intracellular Signaling Peptides and Proteins; C400774:baz protein, Drosophila; D010768:Phosphoserine; D017346:Protein Serine-Threonine Kinases; C532584:Par-6 protein, Drosophila; D011493:Protein Kinase C; D038362:Glycogen Synthase Kinase 3; C472496:Par-1 protein, Drosophila; D054648:Protein Phosphatase 2