title: Phosphotyrosyl phosphatase activator facilitates localization of Miranda through dephosphorylation in dividing neuroblasts.
abstract: The mechanism for the basal targeting of the Miranda (Mira) complex during the asymmetric division of Drosophila neuroblasts (NBs) is yet to be fully understood. We have identified conserved Phosphotyrosyl phosphatase activator (PTPA) as a novel mediator for the basal localization of the Mira complex in larval brain NBs. In mutant Ptpa NBs, Mira remains cytoplasmic during early mitosis and its basal localization is delayed until anaphase. Detailed analyses indicate that PTPA acts independent of and before aPKC to localize Mira. Mechanistically, our data show that the phosphorylation status of the T591 residue determines the subcellular localization of Mira and that PTPA facilitates the dephosphorylation of T591. Furthermore, PTPA associates with the Protein phosphatase 4 complex to mediate localization of Mira. On the basis of these results, a two-step process for the basal localization of Mira during NB division is revealed: cortical association of Mira mediated by the PTPA-PP4 complex is followed by apical aPKC-mediated basal restriction.
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Institute of Molecular and Cell Biology, ASTAR, 138673 Singapore Temasek Life Sciences Laboratory, 117604 Singapore.
authors.forename: Zhen-Xing
authors.initials: ZX
authors.lastname: Huang
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Hongcun
authors.initials: H
authors.lastname: Bao
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Cong
authors.affiliation: Temasek Life Sciences Laboratory, 117604 Singapore.
authors.forename: Huashan
authors.initials: H
authors.lastname: Wang
authors.affiliation: Temasek Life Sciences Laboratory, 117604 Singapore.
authors.forename: Phing Chian
authors.initials: PC
authors.lastname: Chai
authors.affiliation: Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou 310058, China.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Xi
authors.affiliation: Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou 310058, China.
authors.forename: Wanzhong
authors.initials: W
authors.lastname: Ge
authors.affiliation: Department of Genetics, La Trobe Institute for Molecular Science (LIMS), La Trobe University, Melbourne, VIC 3083, Australia.
authors.forename: W Gregory
authors.initials: WG
authors.lastname: Somers
authors.affiliation: Temasek Life Sciences Laboratory, 117604 Singapore Department of Biological Sciences, National University of Singapore, 117543 Singapore.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Temasek Life Sciences Laboratory, 117604 Singapore Department of Biological Sciences, National University of Singapore, 117543 Singapore caiyu@tll.org.sg xhyang@zju.edu.cn.
authors.forename: Yu
authors.initials: Y
authors.lastname: Cai
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, China Institute of Genetics, School of Medicine, Zhejiang University, Hangzhou 310058, China caiyu@tll.org.sg xhyang@zju.edu.cn.
authors.forename: Xiaohang
authors.initials: X
authors.lastname: Yang
mesh_terms: D000818:Animals; D060049:Asymmetric Cell Division / Q000502:physiology; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D004330:Drosophila / Q000196:embryology*; D029721:Drosophila Proteins / Q000378:metabolism*; D058953:Neural Stem Cells / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C107613:Mira protein, Drosophila; C490204:Ptpa protein, Drosophila; C115015:PKC-3 protein; D011493:Protein Kinase C; D010749:Phosphoprotein Phosphatases; C080406:protein phosphatase 4
keywords: Asymmetric cell division; Dephosphorylation of Mira; Drosophila neuroblast; PTPA