Phosphorylation of CRMP2 is involved in proper bifurcation of the apical dendrite of hippocampal CA1 pyramidal neurons

Emi Niisato, Jun Nagai, Naoya Yamashita, Fumio Nakamura, Yoshio Goshima, Toshio Ohshima

    Research output: Contribution to journalArticle

    25 Citations (Scopus)

    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 notobserved 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.

    Original languageEnglish
    Pages (from-to)142-151
    Number of pages10
    JournalDevelopmental Neurobiology
    Volume73
    Issue number2
    DOIs
    Publication statusPublished - 2013 Feb

    Fingerprint

    Pyramidal Cells
    Dendrites
    Phosphorylation
    Semaphorin-3A
    Neurons
    Embryonic Structures
    Phenotype
    Growth Cones
    Brain
    Tubulin
    Axons
    Hippocampus

    Keywords

    • Cdk5
    • Dendrite
    • Sema3A

    ASJC Scopus subject areas

    • Cellular and Molecular Neuroscience
    • Developmental Neuroscience

    Cite this

    Phosphorylation of CRMP2 is involved in proper bifurcation of the apical dendrite of hippocampal CA1 pyramidal neurons. / Niisato, Emi; Nagai, Jun; Yamashita, Naoya; Nakamura, Fumio; Goshima, Yoshio; Ohshima, Toshio.

    In: Developmental Neurobiology, Vol. 73, No. 2, 02.2013, p. 142-151.

    Research output: Contribution to journalArticle

    Niisato, Emi ; Nagai, Jun ; Yamashita, Naoya ; Nakamura, Fumio ; Goshima, Yoshio ; Ohshima, Toshio. / Phosphorylation of CRMP2 is involved in proper bifurcation of the apical dendrite of hippocampal CA1 pyramidal neurons. In: Developmental Neurobiology. 2013 ; Vol. 73, No. 2. pp. 142-151.
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