Phosphotyrosyl phosphatase activator facilitates localization of Miranda through dephosphorylation in dividing neuroblasts

Development. 2016 Jan 1;143(1):35-44. doi: 10.1242/dev.127233. Epub 2015 Nov 19.

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.

Keywords: Asymmetric cell division; Dephosphorylation of Mira; Drosophila neuroblast; PTPA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Asymmetric Cell Division / physiology
  • Cell Cycle Proteins / metabolism*
  • Cell Line
  • Drosophila / embryology*
  • Drosophila Proteins / metabolism*
  • Neural Stem Cells / metabolism*
  • Neurogenesis / physiology*
  • Phosphoprotein Phosphatases / metabolism
  • Phosphorylation
  • Protein Kinase C / metabolism*

Substances

  • Cell Cycle Proteins
  • Drosophila Proteins
  • Mira protein, Drosophila
  • Ptpa protein, Drosophila
  • PKC-3 protein
  • Protein Kinase C
  • Phosphoprotein Phosphatases
  • protein phosphatase 4