Spinophilin facilitates dephosphorylation of doublecortin by PP1 to mediate microtubule bundling at the axonal wrist

Research output: Contribution to journalArticlepeer-review

Authors

  • Stephanie L Bielas
  • Finley F Serneo
  • Thomas J Deerinck
  • Guy A Perkins
  • Patrick B Allen
  • Mark H Ellisman
  • Joseph G Gleeson

Colleges, School and Institutes

External organisations

  • Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.

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.

Details

Original languageEnglish
Pages (from-to)579-91
Number of pages13
JournalCell
Volume129
Issue number3
Publication statusPublished - 4 May 2007

Keywords

  • Actins, Animals, Axons, Cells, Cultured, Corpus Callosum, Cyclin-Dependent Kinase 5, Hippocampus, Humans, Magnetic Resonance Imaging, Male, Mice, Mice, Inbred Strains, Mice, Knockout, Microfilament Proteins, Microtubule-Associated Proteins, Microtubules, Nerve Tissue Proteins, Neurites, Neurons, Neuropeptides, Phosphoprotein Phosphatases, Phosphorylation, Serine, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't