title: CRMP1 and CRMP2 have synergistic but distinct roles in dendritic development.
abstract: Collapsin response mediator protein 2, CRMP2, has been identified as an intracellular signaling mediator for Semaphorin 3A (Sema3A). CRMP2 plays a key role in axon guidance, dendritic morphogenesis, and cell polarization. It has been also implicated in a variety of neurological and psychiatric disorders. However, the in vivo functions of CRMP2 remain unknown. We generated CRMP2 gene-deficient (crmp2(-/-) ) mice. The crmp2(-/-) mice showed irregular development of dendritic spines in cortical neurons. The density of dendritic spines was reduced in the cortical layer V pyramidal neurons of crmp2(-/-) mice as well as in those of sema3A(-/-) and crmp1(-/-) mice. However, no abnormality was found in dendritic patterning in crmp2(-/-) compared to wild-type (WT) neurons. The level of CRMP1 was increased in crmp2(-/-) , but the level of CRMP2 was not altered in crmp1(-/-) compared to WT cortical brain lysates. Dendritic spine density and branching were reduced in double-heterozygous sema3A(+/-) ;crmp2(+/-) and sema3A(+/-) ;crmp1(+/-) mice. The phenotypic defects had no genetic interaction between crmp1 and crmp2. These findings suggest that both CRMP1 and CRMP2 mediate Sema3A signaling to regulate dendritic spine maturation and patterning, but through overlapping and distinct signaling pathways.
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan.|Biological Science and Nursing, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Makihara
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Nakai
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Ohkubo
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan.|JSPS Postdoctoral Fellowship for Research Abroad, Chiyoda-ku, 102-0083, Japan.|Department of Biology, Johns Hopkins University, Baltimore, MD, 21218, USA.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamashita
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Nakamura
authors.affiliation: Animal Resource Development Unit, RIKEN Center for Life Science Technologies, 2-2-3 Minatojima Minami-machi, Chuou-ku, Kobe, 650-0047, Japan.|Genetic Engineering Team, RIKEN Center for Life Science Technologies, 2-2-3 Minatojima Minami-machi, Chuou-ku, Kobe, 650-0047, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kiyonari
authors.affiliation: Genetic Engineering Team, RIKEN Center for Life Science Technologies, 2-2-3 Minatojima Minami-machi, Chuou-ku, Kobe, 650-0047, Japan.
authors.forename: Go
authors.initials: G
authors.lastname: Shioi
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Aoi
authors.initials: A
authors.lastname: Jitsuki-Takahashi
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan.|Department of Neurology and Stroke Medicine, Graduate School of Medicine, Yokohama City University, Yokohama, 236-0004, Japan.
authors.forename: Haruko
authors.initials: H
authors.lastname: Nakamura
authors.affiliation: Department of Neurology and Stroke Medicine, Graduate School of Medicine, Yokohama City University, Yokohama, 236-0004, Japan.
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Tanaka
authors.affiliation: Biological Science and Nursing, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan.
authors.forename: Tomoko
authors.initials: T
authors.lastname: Akase
authors.affiliation: Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL, USA.
authors.forename: Pappachan
authors.initials: P
authors.lastname: Kolattukudy
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Graduate School of Medicine, Yokohama City University, 3-9 Fuku-ura, Kanazawa-ku, Yokohama, 236-0004, Japan. goshima@med.yokohama-cu.ac.jp.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
mesh_terms: D000818:Animals; D002452:Cell Count; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003712:Dendrites / Q000378:metabolism / Q000502:physiology*; D005260:Female; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D055495:Neurogenesis / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D040121:Semaphorin-3A / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D000098855:Collapsin Response Mediator Protein 1
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D040121:Semaphorin-3A; C502872:Crmp1 protein, mouse; D000098855:Collapsin Response Mediator Protein 1; C095114:collapsin response mediator protein-2