Hook3 interacts with PCM1 to regulate pericentriolar material assembly and the timing of neurogenesis

Neuron. 2010 Jan 28;65(2):191-203. doi: 10.1016/j.neuron.2010.01.011.

Abstract

Centrosome functions are important in multiple brain developmental processes. Proper functioning of the centrosome relies on assembly of protein components into the pericentriolar material. This dynamic assembly is mediated by the trafficking of pericentriolar satellites, which are comprised of centrosomal proteins. Here we demonstrate that trafficking of pericentriolar satellites requires the interaction between Hook3 and Pericentriolar Material 1 (PCM1). Hook3, previously shown to link the centrosome and the nucleus in C. elegans, is recruited to pericentriolar satellites through interaction with PCM1, a protein associated with schizophrenia. Disruption of the Hook3-PCM1 interaction in vivo impairs interkinetic nuclear migration, a featured behavior of embryonic neural progenitors. This in turn leads to overproduction of neurons and premature depletion of the neural progenitor pool in the developing neocortex. These results underscore the importance of centrosomal assembly in neurogenesis and provide potential insights into the etiology of brain developmental diseases related to the centrosome dysfunction.

Publication types

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

MeSH terms

  • Animals
  • Autoantigens / metabolism
  • Autoantigens / physiology*
  • Cell Cycle Proteins / metabolism
  • Cell Cycle Proteins / physiology*
  • Cell Nucleus / physiology
  • Centrosome / metabolism
  • Centrosome / physiology*
  • Cerebral Cortex / cytology
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / physiology
  • Female
  • Humans
  • Mice
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / physiology*
  • NIH 3T3 Cells
  • Neurogenesis / physiology*
  • Pregnancy
  • Protein Binding / physiology
  • Stem Cells / physiology
  • Time Factors

Substances

  • Autoantigens
  • Cell Cycle Proteins
  • Microtubule-Associated Proteins
  • PCM1 protein, human
  • hook3 protein, human