title: Phosphorylation of CRMP2 (collapsin response mediator protein 2) is involved in proper dendritic field organization.
abstract: Collapsin response mediator proteins (CRMPs) are intracellular proteins that mediate signals for several extracellular molecules, such as Semaphorin3A and neurotrophins. The phosphorylation of CRMP1 and CRMP2 by Cdk5 at Ser522 is involved in axonal guidance and spine development. Here, we found that the Ser522-phosphorylated CRMP1 and/or CRMP2 are enriched in the dendrites of cultured cortical neurons and P7 cortical section. To determine the physiological role of CRMPs in dendritic development, we generated CRMP2 knock-in mutant mice (crmp2ki/ki) in which the Ser residue at 522 was replaced with Ala. Strikingly, the cortical basal dendrites of double mutant crmp2ki/ki and crmp1-/- mice exhibited severe abnormal dendritic patterning, which we defined as "curling phenotype." These findings demonstrate that the function of CRMP1 and CRMP2 synergistically control dendritic projection, and the phosphorylation of CRMP2 at Ser522 is essential for proper dendritic field organization in vivo.
authors.affiliation: Department of Molecular Pharmacology and Neurobiology, Yokohama City University Graduate School of Medicine, Yokohama 236-0004, Japan.
authors.forename: Naoya
authors.initials: N
authors.lastname: Yamashita
authors.forename: Toshio
authors.initials: T
authors.lastname: Ohshima
authors.forename: Fumio
authors.initials: F
authors.lastname: Nakamura
authors.forename: Papachan
authors.initials: P
authors.lastname: Kolattukudy
authors.forename: Jérôme
authors.initials: J
authors.lastname: Honnorat
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Mikoshiba
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Goshima
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5 / Q000235:genetics; D003712:Dendrites / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D005260:Female; D055879:Gene Knock-In Techniques; D036341:Intercellular Signaling Peptides and Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; C095114:collapsin response mediator protein-2; D051360:Cyclin-Dependent Kinase 5; C495906:Cdk5 protein, mouse