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 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.
Bielas
Stephanie L
SL
Neurobiology Section, Division of Biological Sciences, University of California, San Diego, La Jolla, CA 92093, USA.
Serneo
Finley F
FF
Chechlacz
Magdalena
M
Deerinck
Thomas J
TJ
Perkins
Guy A
GA
Allen
Patrick B
PB
Ellisman
Mark H
MH
Gleeson
Joseph G
JG
D000199:Actins / Q000378:metabolism; D000818:Animals; D001369:Axons / Q000378:metabolism*; D002478:Cells, Cultured; D003337:Corpus Callosum / Q000033:anatomy & histology; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D016501:Neurites / Q000378:metabolism; D009474:Neurons / Q000378:metabolism; D009479:Neuropeptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D012694:Serine / Q000378:metabolism; D000099273:Neurabins
D000199:Actins; D051360:Cyclin-Dependent Kinase 5; D000089622:Doublecortin Domain Proteins; D000089662:Doublecortin Protein; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D010749:Phosphoprotein Phosphatases; D012694:Serine; D000099273:Neurabins; C000714328:DCX protein, human; C000714847:Dcx protein, mouse