TY - JOUR
T1 - Phosphorylation of CRMP2 is required for migration and positioning of Purkinje cells
T2 - Redundant roles of CRMP1 and CRMP4
AU - Yamazaki, Yuki
AU - Nagai, Jun
AU - Akinaga, Satoshi
AU - Koga, Yumeno
AU - Hasegawa, Masaya
AU - Takahashi, Miyuki
AU - Yamashita, Naoya
AU - Kolattukudy, Papachan
AU - Goshima, Yoshio
AU - Ohshima, Toshio
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research on Priority Areas from The Ministry of Education, Culture, Sports, Science and Technology (no. 26430043 to T.O and no. 17082006 to Y.G.) and Core Research for Evolutional Science and technology ( CREST ) of Japan Science and Technology Agency (Y.G.).
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2020/6/1
Y1 - 2020/6/1
N2 - Proper migration and positioning of Purkinje cells are important for formation of the developing cerebellum. Although several cyclin-dependent kinase 5 (Cdk5) substrates are known to be critical for ordered neuronal migration, there are no reports of mutant mouse-based, in vivo studies on the function of Cdk5-phosphorylation substrates in migration of Purkinje cells. We focused on the analysis of collapsin response mediator protein 2 (CRMP2), one of the Cdk5 substrates, because a previous study reported migration defects of cortical neurons with shRNA-mediated knockdown of CRMP2. However, CRMP2 KI/KI mice, in which Cdk5-phosphorylation is inhibited, showed little defects in Purkinje cell migration and positioning. We hypothesized compensatory redundant functions of the other CRMPs, and analyzed the migration and positioning of Purkinje cells in the cerebellum in every combination of CRMP1 knockout (KO), CRMP2 KI/KI, and CRMP4 KO mice. Severe disturbance of migration and positioning of Purkinje cells were observed in the triple mutant mice. We also found motor coordination defects in the triple CRMPs mutant mice. These results suggest the importance of both, phosphorylation of CRMP2 by Cdk5 and the redundant functions of CRMP1 and CRMP4 in proper migration and positioning of Purkinje cells in developing cerebellum.
AB - Proper migration and positioning of Purkinje cells are important for formation of the developing cerebellum. Although several cyclin-dependent kinase 5 (Cdk5) substrates are known to be critical for ordered neuronal migration, there are no reports of mutant mouse-based, in vivo studies on the function of Cdk5-phosphorylation substrates in migration of Purkinje cells. We focused on the analysis of collapsin response mediator protein 2 (CRMP2), one of the Cdk5 substrates, because a previous study reported migration defects of cortical neurons with shRNA-mediated knockdown of CRMP2. However, CRMP2 KI/KI mice, in which Cdk5-phosphorylation is inhibited, showed little defects in Purkinje cell migration and positioning. We hypothesized compensatory redundant functions of the other CRMPs, and analyzed the migration and positioning of Purkinje cells in the cerebellum in every combination of CRMP1 knockout (KO), CRMP2 KI/KI, and CRMP4 KO mice. Severe disturbance of migration and positioning of Purkinje cells were observed in the triple mutant mice. We also found motor coordination defects in the triple CRMPs mutant mice. These results suggest the importance of both, phosphorylation of CRMP2 by Cdk5 and the redundant functions of CRMP1 and CRMP4 in proper migration and positioning of Purkinje cells in developing cerebellum.
KW - Cerebellum
KW - Neuronal migration
KW - Phosphorylation
KW - Purkinje cell
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U2 - 10.1016/j.brainres.2020.146762
DO - 10.1016/j.brainres.2020.146762
M3 - Article
C2 - 32156571
AN - SCOPUS:85081692037
SN - 0006-8993
VL - 1736
JO - Brain Research
JF - Brain Research
M1 - 146762
ER -