title: DCLK1 phosphorylates the microtubule-associated protein MAP7D1 to promote axon elongation in cortical neurons.
abstract: Doublecortin-like kinase 1 (DCLK1) is a member of the neuronal microtubule-associated doublecortin (DCX) family and functions in multiple stages of neural development including radial migration and axon growth of cortical neurons. DCLK1 is suggested to play the roles in part through its protein kinase activity, yet the kinase substrates of DCLK1 remain largely unknown. Here we have identified MAP7D1 (microtubule-associated protein 7 domain containing 1) as a novel substrate of DCLK1 by using proteomic analysis. MAP7D1 is expressed in developing cortical neurons, and knockdown of MAP7D1 in layer 2/3 cortical neurons results in a significant impairment of callosal axon elongation, but not of radial migration, in corticogenesis. We have further defined the serine 315 (Ser 315) of MAP7D1 as a DCLK1-induced phosphorylation site and shown that overexpression of a phosphomimetic MAP7D1 mutant in which Ser 315 is substituted with glutamic acid (MAP7D1 S315E), but not wild-type MAP7D1, fully rescues the axon elongation defects in Dclk1 knockdown neurons. These data demonstrate that DCLK1 phosphorylates MAP7D1 on Ser 315 to facilitate axon elongation of cortical neurons. © 2016 Wiley Periodicals, Inc. Develop Neurobiol 77: 419-437, 2017.
authors: Department of Biological Sciences, School of Science, The University of Tokyo, Tokyo, 113-0033, Japan.|Department of Cell Biology, Osaka Bioscience Institute, Osaka, 565-0874, Japan.
authors: Hiroyuki
authors: H
authors: Koizumi
authors: Department of Cell Biology, Osaka Bioscience Institute, Osaka, 565-0874, Japan.|Department of Bioscience, Nara Institute of Science and Technology, Nara, 630-0192, Japan.
authors: Hiromi
authors: H
authors: Fujioka
authors: Department of Biological Sciences, School of Science, The University of Tokyo, Tokyo, 113-0033, Japan.|Department of Cell Biology, Osaka Bioscience Institute, Osaka, 565-0874, Japan.
authors: Kazuya
authors: K
authors: Togashi
authors: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, 92037.
authors: James
authors: J
authors: Thompson
authors: Department of Chemical Physiology, The Scripps Research Institute, La Jolla, California, 92037.
authors: John R
authors: JR
authors: Yates
authors: Laboratory of Pediatric Brain Diseases, Howard Hughes Medical Institute, The Rockefeller University, New York, New York, 10021-6399.
authors: Joseph G
authors: JG
authors: Gleeson
authors: Department of Biological Sciences, School of Science, The University of Tokyo, Tokyo, 113-0033, Japan.|Department of Cell Biology, Osaka Bioscience Institute, Osaka, 565-0874, Japan.|Department of Bioscience, Nara Institute of Science and Technology, Nara, 630-0192, Japan.
authors: Kazuo
authors: K
authors: Emoto
mesh_terms: D000818:Animals; D005260:Female; D051379:Mice; D011247:Pregnancy; D001369:Axons / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D000089662:Doublecortin Protein; D000089742:Doublecortin-Like Kinases; D018507:Gene Expression Regulation, Developmental; D047908:Intracellular Signaling Peptides and Proteins; D008810:Mice, Inbred C57BL; D008813:Mice, Inbred ICR; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D040901:Proteomics
chemical_list: C117347:DCLK1 protein, human; C485525:Dclk1 protein, mouse; C000714847:Dcx protein, mouse; D000089662:Doublecortin Protein; D000089742:Doublecortin-Like Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008869:Microtubule-Associated Proteins; D017346:Protein Serine-Threonine Kinases; C000721970:MAP7 protein, mouse
keywords: axon elongation; cortical neuron; doublecortin-like kinase; in utero electroporation; microtubule-associated protein