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

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 i...

Full description

Saved in:
Bibliographic Details
Published in:Cell 2007-05, Vol.129 (3), p.579-591
Main Authors: Bielas, Stephanie L., Serneo, Finley F., Chechlacz, Magdalena, Deerinck, Thomas J., Perkins, Guy A., Allen, Patrick B., Ellisman, Mark H., Gleeson, Joseph G.
Format: Article
Language:English
Subjects:
Actins - metabolism
Animals
Axons - metabolism
CELLBIO
Cells, Cultured
Corpus Callosum - anatomy & histology
Cyclin-Dependent Kinase 5 - metabolism
DEVBIO
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
MOLNEURO
Nerve Tissue Proteins - genetics
Nerve Tissue Proteins - metabolism
Neurites - metabolism
Neurons - metabolism
Neuropeptides - chemistry
Neuropeptides - genetics
Neuropeptides - metabolism
Phosphoprotein Phosphatases - metabolism
Phosphorylation
Serine - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2007.03.023