NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein

被引:410
作者
Niethammer, M
Smith, DS
Ayala, R
Peng, JM
Ko, J
Lee, MS
Morabito, M
Tsai, LH
机构
[1] Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA
[2] Harvard Univ, Sch Med, Howard Hughes Med Inst, Boston, MA 02115 USA
基金
美国国家卫生研究院;
关键词
D O I
10.1016/S0896-6273(00)00147-1
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Disruption of one allele of the LIS1 gene causes a severe developmental brain abnormality, type I lissencephaly. In Aspergillus nidulans, the LIS1 homolog, NUDE, and cytoplasmic dynein are genetically linked and regulate nuclear movements during hyphal growth. Recently, we demonstrated that mammalian LIS1 regulates dynein functions. Here we characterize NUDEL, a novel LIS1-interacting protein with sequence homology to gene products also implicated in nuclear distribution in fungi. Like LIS1, NUDEL is robustly expressed in brain, enriched at centrosomes and neuronal growth cones, and interacts with cytoplasmic dynein. Furthermore, NUDEL is a substrate of Cdk5, a kinase known to be critical during neuronal migration. Inhibition of Cdk5 modifies NUDEL distribution in neurons and affects neuritic morphology. Our findings point to crosstalk between two prominent pathways that regulate neuronal migration.
引用
收藏
页码:697 / 711
页数:15
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