NUDEL is a novel Cdk5 substrate that associates with LIS1 and cytoplasmic dynein.
Disruption of one allele of the LIS1 gene causes a severe developmental brain abnormality, type I lissencephaly. In Aspergillus nidulans, the LIS1 homolog, NUDF, 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 cross-talk between two prominent pathways that regulate neuronal migration.
Niethammer
M
M
Department of Pathology, Harvard Medical School, 200 Longwood Avenue, Boston, Massachussetts 02115, USA.
Smith
D S
DS
Ayala
R
R
Peng
J
J
Ko
J
J
Lee
M S
MS
Morabito
M
M
Tsai
L H
LH
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D001369:Axons / Q000378:metabolism / Q000648:ultrastructure; D001483:Base Sequence; D001921:Brain / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D017124:Conserved Sequence; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005656:Fungal Proteins / Q000235:genetics; D020439:Growth Cones / Q000378:metabolism; D006801:Humans; D008297:Male; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008969:Molecular Sequence Data; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009928:Organ Specificity; D010750:Phosphoproteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D013737:Testis / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D008869:Microtubule-Associated Proteins; C421108:NDEL1 protein, human; D010750:Phosphoproteins; C121041:RO-11 protein, Neurospora crassa; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; D018844:Cyclin-Dependent Kinases; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; D004398:Dyneins