Protein phosphatase 2A negatively regulates aPKC signaling by modulating phosphorylation of Par-6 in Drosophila neuroblast asymmetric divisions.
Drosophila neural stem cells or neuroblasts undergo typical asymmetric cell division. An evolutionally conserved protein complex, comprising atypical protein kinase C (aPKC), Bazooka (Par-3) and Par-6, organizes cell polarity to direct these asymmetric divisions. Aurora-A (AurA) is a key molecule that links the divisions to the cell cycle. Upon its activation in metaphase, AurA phosphorylates Par-6 and activates aPKC signaling, triggering the asymmetric organization of neuroblasts. Little is known, however, about how such a positive regulatory cue is counteracted to coordinate aPKC signaling with other cellular processes. During a mutational screen using the Drosophila compound eye, we identified microtubule star (mts), which encodes a catalytic subunit of protein phosphatase 2A (PP2A), as a negative regulator for aPKC signaling. Impairment of mts function causes defects in neuroblast divisions, as observed in lethal (2) giant larvae (lgl) mutants. mts genetically interacts with par-6 and lgl in a cooperative manner in asymmetric neuroblast division. Furthermore, Mts tightly associates with Par-6 and dephosphorylates AurA-phosphorylated Par-6. Our genetic and biochemical evidence indicates that PP2A suppresses aPKC signaling by promoting Par-6 dephosphorylation in neuroblasts, which uncovers a novel balancing mechanism for aPKC signaling in the regulation of asymmetric cell division.
Ogawa
Hironori
H
Laboratory for Cell Asymmetry, RIKEN Center for Developmental Biology, Kobe, Hyogo 650-0047, Japan.
Ohta
Nao
N
Moon
Woongjoon
W
Matsuzaki
Fumio
F
D000818:Animals; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D016764:Cell Polarity; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000166:cytology / Q000196:embryology / Q000201:enzymology* / Q000235:genetics; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000201:enzymology; D004847:Epithelial Cells / Q000166:cytology / Q000378:metabolism; D005260:Female; D017344:Genes, Insect; D008954:Models, Biological; D009474:Neurons / Q000166:cytology* / Q000201:enzymology; D006080:Ovarian Follicle / Q000166:cytology; D010641:Phenotype; D010766:Phosphorylation; D011485:Protein Binding; D011493:Protein Kinase C / Q000378:metabolism*; D054648:Protein Phosphatase 2 / Q000378:metabolism; D021381:Protein Transport; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C107613:Mira protein, Drosophila; D025521:Tumor Suppressor Proteins; C081435:l(2)gl protein, Drosophila; C529534:mts protein, Drosophila; C115015:PKC-3 protein; C532584:Par-6 protein, Drosophila; D011493:Protein Kinase C; D054648:Protein Phosphatase 2