PAR-1 phosphorylates Mind bomb to promote vertebrate neurogenesis

Dev Cell. 2009 Aug;17(2):222-33. doi: 10.1016/j.devcel.2009.06.010.

Abstract

Generation of neurons in the vertebrate central nervous system requires a complex transcriptional regulatory network and signaling processes in polarized neuroepithelial progenitor cells. Here we demonstrate that neurogenesis in the Xenopus neural plate in vivo and mammalian neural progenitors in vitro involves intrinsic antagonistic activities of the polarity proteins PAR-1 and aPKC. Furthermore, we show that Mind bomb (Mib), a ubiquitin ligase that promotes Notch ligand trafficking and activity, is a crucial molecular substrate for PAR-1. The phosphorylation of Mib by PAR-1 results in Mib degradation, repression of Notch signaling, and stimulation of neuronal differentiation. These observations suggest a conserved mechanism for neuronal fate determination that might operate during asymmetric divisions of polarized neural progenitor cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Differentiation / physiology
  • Cell Line
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / metabolism
  • Mice
  • Molecular Sequence Data
  • Neurogenesis / physiology*
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / metabolism
  • Protein Kinase C / genetics
  • Protein Kinase C / metabolism
  • Protein-Serine-Threonine Kinases / genetics
  • Protein-Serine-Threonine Kinases / metabolism*
  • Receptors, Notch / genetics
  • Receptors, Notch / metabolism
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Sequence Alignment
  • Signal Transduction / physiology
  • Stem Cells / physiology
  • Ubiquitin-Protein Ligases / genetics
  • Ubiquitin-Protein Ligases / metabolism*
  • Ubiquitination
  • Vertebrates / embryology*
  • Xenopus Proteins / genetics
  • Xenopus Proteins / metabolism*
  • Xenopus laevis / embryology*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Oligonucleotides, Antisense
  • Receptors, Notch
  • Recombinant Fusion Proteins
  • Xenopus Proteins
  • Ubiquitin-Protein Ligases
  • mib1 protein, Xenopus
  • MARK3 protein, Xenopus
  • Protein-Serine-Threonine Kinases
  • PKC-3 protein
  • Protein Kinase C