Tyrosine hydroxylase expression and Cdk5 kinase activity in ataxic cerebellum.
Ataxia has been associated with abnormalities in neuronal differentiation and migration, which are regulated by Cyclin-dependent kinase 5 (Cdk5). The cerebellum of mice lacking Cdk5 or its activator, p35, resembles those of ataxic reeler and scrambler mice, suggesting that Cdk5 may contribute to ataxic pathology. As with other ataxic mice, the pogo/pogo mouse shows aberrant cerebellar tyrosine hydroxylase (TH) expression. Since Cdk5 phosphorylates and upregulates TH expression, we sought to analyze (i) Cdk5 activity in the pogo cerebellum, which exhibits abnormal TH expression, and (ii) TH expression in the cerebellum of p35-/- and p39-/- mice, which display reduced Cdk5 activity. Interestingly, we found that increased TH expression in the pogo cerebellum coincided with reduced Cdk5 activity. However, reduced Cdk5 activity in both p35-/- and p39-/- cerebellum did not correspond to defects in TH expression. Together, these suggest that abnormal TH expression in the cerebellum might be regulated by mechanisms other than Cdk5 activity.
Cheung
K-John J
KJ
Department of Cell Biology and Anatomy, Southern Alberta Cancer Research Institute and Hotchkiss Brain Institute, The University of Calgary, Heritage Medical Research Building, Calgary, AB, Canada, T2N4N1.
Rosales
Jesusa L
JL
Lee
Byung-Chul
BC
Jeong
Young-Gil
YG
Lee
Ki-Young
KY
D000818:Animals; D002524:Cerebellar Ataxia / Q000201:enzymology*; D051360:Cyclin-Dependent Kinase 5 / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000172:deficiency; D010766:Phosphorylation; D010770:Phosphotransferases / Q000172:deficiency; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism
C108298:Cdk5 activator p39; C492236:Cdk5r1 protein, mouse; D009419:Nerve Tissue Proteins; D016875:tau Proteins; D014446:Tyrosine 3-Monooxygenase; D010770:Phosphotransferases; D051360:Cyclin-Dependent Kinase 5