title: Phosphorylation of CRMP2 by Cdk5 Regulates Dendritic Spine Development of Cortical Neuron in the Mouse Hippocampus.
abstract: Proper density and morphology of dendritic spines are important for higher brain functions such as learning and memory. However, our knowledge about molecular mechanisms that regulate thedevelopment and maintenance of dendritic spines is limited. We recently reported that cyclin-dependent kinase 5 (Cdk5) is required for the development and maintenance of dendritic spines of cortical neurons in the mouse brain. Previous in vitro studies have suggested the involvement of Cdk5 substrates in the formation of dendritic spines; however, their role in spine development has not been tested in vivo. Here, we demonstrate that Cdk5 phosphorylates collapsin response mediator protein 2 (CRMP2) in the dendritic spines of cultured hippocampal neurons and in vivo in the mouse brain. When we eliminated CRMP2 phosphorylation in CRMP2(KI/KI) mice, the densities of dendritic spines significantly decreased in hippocampal CA1 pyramidal neurons in the mouse brain. These results indicate that phosphorylation of CRMP2 by Cdk5 is important for dendritic spine development in cortical neurons in the mouse hippocampus.
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Jin
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Kodai
authors.initials: K
authors.lastname: Sasamoto
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Nagai
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamazaki
authors.affiliation: Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Kenta
authors.initials: K
authors.lastname: Saito
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Graduate School of Medicine, Yokohama City University, Yokohama 236-0004, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
authors.affiliation: Laboratory for Neurophysiology, Department of Life Science and Medical Bioscience, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Takafumi
authors.initials: T
authors.lastname: Inoue
authors.affiliation: Laboratory for Molecular Brain Science, Department of Life Science and Medical Bioscience, Waseda University, Tokyo 162-8480, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohshima
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics / Q000378:metabolism*; D049229:Dendritic Spines / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C095114:collapsin response mediator protein-2; D051360:Cyclin-Dependent Kinase 5
references.citation: J Neurosci. 2002 May 1;22(9):3700-7
references.pmid: 11978846
references.citation: Nat Cell Biol. 2002 Aug;4(8):583-91
references.pmid: 12134159
references.citation: Eur J Neurosci. 2003 Jun;17(11):2329-43
references.pmid: 12814366
references.citation: J Cell Biol. 2003 Nov 24;163(4):813-24
references.pmid: 14623869
references.citation: J Neurosci. 2004 Jan 28;24(4):865-76
references.pmid: 14749431
references.citation: Brain Res. 1978 Oct 20;155(1):108-12
references.pmid: 688003
references.citation: Neuropsychologia. 1990;28(6):517-27
references.pmid: 2203993
references.citation: J Comp Neurol. 1993 Jul 1;333(1):53-67
references.pmid: 8340496
references.citation: Nature. 1995 Aug 10;376(6540):509-14
references.pmid: 7637782
references.citation: J Biol Chem. 1996 Aug 30;271(35):21108-13
references.pmid: 8702879
references.citation: J Neurosci. 1996 Oct 1;16(19):6197-207
references.pmid: 8815901
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):11173-8
references.pmid: 8855328
references.citation: Cell. 2005 Jan 14;120(1):137-49
references.pmid: 15652488
references.citation: Genes Cells. 2005 Feb;10(2):165-79
references.pmid: 15676027
references.citation: J Neurochem. 2005 Aug;94(4):917-25
references.pmid: 15992381
references.citation: Mol Cell Biol. 2005 Nov;25(22):9973-84
references.pmid: 16260611
references.citation: Nature. 2006 Aug 17;442(7104):814-7
references.pmid: 16862120
references.citation: Nat Neurosci. 2007 Jan;10(1):67-76
references.pmid: 17143272
references.citation: Nat Neurosci. 2007 Jul;10(7):880-6
references.pmid: 17529984
references.citation: J Neurosci. 2007 Nov 14;27(46):12546-54
references.pmid: 18003833
references.citation: Biochim Biophys Acta. 2009 Aug;1792(8):741-5
references.pmid: 19442718
references.citation: Nat Neurosci. 2011 Mar;14(3):285-93
references.pmid: 21346746
references.citation: PLoS One. 2011;6(9):e25735
references.pmid: 21984943
references.citation: J Immunol. 2012 Feb 1;188(3):1222-33
references.pmid: 22227566
references.citation: J Neurosci. 2012 Jan 25;32(4):1360-5
references.pmid: 22279220
references.citation: Neuron. 2012 Aug 23;75(4):675-87
references.pmid: 22920258
references.citation: Dev Neurobiol. 2012 Nov;72(11):1447-57
references.pmid: 22234963
references.citation: Nat Neurosci. 2012 Nov;15(11):1506-15
references.pmid: 23064382
references.citation: PLoS One. 2014;9(3):e92291
references.pmid: 24637538
references.citation: Mol Brain. 2014;7:82
references.pmid: 25404232
references.citation: J Biol Chem. 2015 Jun 5;290(23):14637-46
references.pmid: 25903132
references.citation: Neural Plast. 2015;2015:947423
references.pmid: 26064693
references.citation: Cereb Cortex. 2016 Mar;26(3):967-76
references.pmid: 25404468
references.citation: J Biol Chem. 2000 Sep 1;275(35):27291-302
references.pmid: 10851247
references.citation: Neuron. 2000 Oct;28(1):41-51
references.pmid: 11086982
references.citation: J Biol Chem. 2000 Dec 1;275(48):37957-65
references.pmid: 10956643
references.citation: Proc Natl Acad Sci U S A. 2001 Oct 23;98(22):12742-7
references.pmid: 11675505