Spinophilin Facilitates Dephosphorylation of Doublecortin by PP1 to Mediate Microtubule Bundling at the Axonal Wrist

Cell. 2007 May 4;129(3):579-91. doi: 10.1016/j.cell.2007.03.023.

Abstract

The axonal shafts of neurons contain bundled microtubules, whereas extending growth cones contain unbundled microtubule filaments, suggesting that localized activation of microtubule-associated proteins (MAP) at the transition zone may bundle these filaments during axonal growth. Dephosphorylation is thought to lead to MAP activation, but specific molecular pathways have remained elusive. We find that Spinophilin, a Protein-phosphatase 1 (PP1) targeting protein, is responsible for the dephosphorylation of the MAP Doublecortin (Dcx) Ser 297 selectively at the "wrist" of growing axons, leading to activation. Loss of activity at the "wrist" is evident as an impaired microtubule cytoskeleton along the shaft. These findings suggest that spatially restricted adaptor-specific MAP reactivation through dephosphorylation is important in organization of the neuronal cytoskeleton.

Publication types

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

MeSH terms

  • Actins / metabolism
  • Animals
  • Axons / metabolism*
  • Cells, Cultured
  • Corpus Callosum / anatomy & histology
  • Cyclin-Dependent Kinase 5 / metabolism
  • Hippocampus / metabolism
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mice
  • Mice, Inbred Strains
  • Mice, Knockout
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism*
  • Microtubule-Associated Proteins / chemistry
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism*
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / metabolism*
  • Neurites / metabolism
  • Neurons / metabolism
  • Neuropeptides / chemistry
  • Neuropeptides / genetics
  • Neuropeptides / metabolism*
  • Phosphoprotein Phosphatases / metabolism*
  • Phosphorylation
  • Serine / metabolism

Substances

  • Actins
  • Microfilament Proteins
  • Microtubule-Associated Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • doublecortin protein
  • neurabin
  • Serine
  • Cyclin-Dependent Kinase 5
  • Phosphoprotein Phosphatases