Kawauchi Takeshi, Chihama Kaori, Nishimura Yoshiaki V, Nabeshima Yo-ichi, Hoshino Mikio
Department of Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Biochem Biophys Res Commun. 2005 May 27;331(1):50-5. doi: 10.1016/j.bbrc.2005.03.132.
Mode I phosphorylated MAP1B is observed in developing and pathogenic brains. Although Cdk5 has been believed to phosphorylate MAP1B in the developing cerebral cortex, we show that a Cdk5 inhibitor does not suppress mode I phosphorylation of MAP1B in primary and slice cultures, while a JNK inhibitor does. Coincidently, an increase in phosphorylated MAP1B was not observed in COS7 cells when Cdk5 was cotransfected with p35, but this did occur with p25 which is specifically produced in pathogenic brains. Our primary culture studies showed an involvement of Cdk5 in regulating microtubule dynamics without affecting MAP1B phosphorylation status. The importance of regulating microtubule dynamics in neuronal migration was also demonstrated by in utero electroporation experiments. These findings suggest that mode I phosphorylation of MAP1B is facilitated by JNK but not Cdk5/p35 in the developing cerebral cortex and by Cdk5/p25 in pathogenic brains, contributing to various biological events.
在发育中的大脑和致病大脑中可观察到I型磷酸化的MAP1B。尽管人们一直认为Cdk5在发育中的大脑皮层中使MAP1B磷酸化，但我们发现，在原代培养物和脑片培养物中，Cdk5抑制剂并不能抑制MAP1B的I型磷酸化，而JNK抑制剂则可以。巧合的是，当Cdk5与p35共转染时，在COS7细胞中未观察到磷酸化的MAP1B增加，但当与在致病大脑中特异性产生的p25共转染时则会出现这种情况。我们的原代培养研究表明，Cdk5参与调节微管动力学，但不影响MAP1B的磷酸化状态。子宫内电穿孔实验也证明了调节微管动力学在神经元迁移中的重要性。这些发现表明，在发育中的大脑皮层中，MAP1B的I型磷酸化由JNK而非Cdk5/p35促进，而在致病大脑中则由Cdk5/p25促进，这促成了各种生物学事件。
