title: Phosphorylation of CRMP2 is involved in proper bifurcation of the apical dendrite of hippocampal CA1 pyramidal neurons.
abstract: The neural circuit in the hippocampus is important for higher brain functions. Dendrites of CA1 pyramidal neurons mainly receive input from the axons of CA3 pyramidal neurons in this neural circuit. A CA1 pyramidal neuron has a single apical dendrite and multiple basal dendrites. In wild-type mice, most of CA1 pyramidal neurons extend a single trunk, or alternatively, the apical dendrite bifurcates into two daughter trunks at the stratum radiatum layer. We previously reported the proximal bifurcation phenotype in Sema3A-/-, p35-/-, and CRMP4-/- mice. Cdk5/p35 phosphorylates CRMP2 at Ser522, and inhibition of this phosphorylation suppressed Sema3A-induced growth cone collapse. In this study, we analyzed the bifurcation points of the apical dendrites of hippocampal CA1 pyramidal neurons in CRMP2KI/KI mice in which the Cdk5/p35-phosphorylation site Ser522 was mutated into an Ala residue. The proximal bifurcation phenotype was not observed in CRMP2KI/KI mice; however, severe proximal bifurcation of apical dendrites was found in CRMP2KI/KI;CRMP4-/- mice. Cultured hippocampal neurons from CRMP2KI/KI and CRMP2KI/KI;CRMP4-/- embryos showed an increased number of dendritic branching points compared to those from wild-type embryos. Sema3A increased the number of branching points and the total length of dendrites in wild-type hippocampal neurons, but these effects of Sema3A for dendrites were not observed in CRMP2KI/KI and CRMP2KI/KI;CRMP4-/-hippocampal neurons. Binding of CRMP2 to tubulin increased in both CRMP2KI/KI and CRMP2KI/KI:CRMP4-/- brain lysates. These results suggest that CRMP2 and CRMP4 synergistically regulate dendritic development, and CRMP2 phosphorylation is critical for proper bifurcation of apical dendrite of CA1 pyramidal neurons.
authors: Department of Life Science and Medical Bioscience, Waseda University, Tokyo 162-8480, Japan.
authors: Emi
authors: E
authors: Niisato
authors: Jun
authors: J
authors: Nagai
authors: Naoya
authors: N
authors: Yamashita
authors: Fumio
authors: F
authors: Nakamura
authors: Yoshio
authors: Y
authors: Goshima
authors: Toshio
authors: T
authors: Ohshima
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001923:Brain Chemistry; D056547:CA1 Region, Hippocampal / Q000166:cytology* / Q000196:embryology; D002478:Cells, Cultured; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism; D003712:Dendrites / Q000502:physiology*; D049452:Green Fluorescent Proteins / Q000235:genetics; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D017966:Pyramidal Cells / Q000502:physiology*; D040121:Semaphorin-3A / Q000494:pharmacology; D014404:Tubulin / Q000235:genetics
chemical_list: C526904:Dpysl3 protein, mouse; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D040121:Semaphorin-3A; D014404:Tubulin; C095114:collapsin response mediator protein-2; D049452:Green Fluorescent Proteins; D051360:Cyclin-Dependent Kinase 5