A LIS1/NUDEL/cytoplasmic dynein heavy chain complex in the developing and adult nervous system.
Mutations in mammalian Lis1 (Pafah1b1) result in neuronal migration defects. Several lines of evidence suggest that LIS1 participates in pathways regulating microtubule function, but the molecular mechanisms are unknown. Here, we demonstrate that LIS1 directly interacts with the cytoplasmic dynein heavy chain (CDHC) and NUDEL, a murine homolog of the Aspergillus nidulans nuclear migration mutant NudE. LIS1 and NUDEL colocalize predominantly at the centrosome in early neuroblasts but redistribute to axons in association with retrograde dynein motor proteins. NUDEL is phosphorylated by Cdk5/p35, a complex essential for neuronal migration. NUDEL and LIS1 regulate the distribution of CDHC along microtubules, and establish a direct functional link between LIS1, NUDEL, and microtubule motors. These results suggest that LIS1 and NUDEL regulate CDHC activity during neuronal migration and axonal retrograde transport in a Cdk5/p35-dependent fashion.
Sasaki
S
S
Shirakawa Institute of Animal Genetics, Odakura Nishigo Nishishirakawa, 961-8061, Fukushima, Japan.
Shionoya
A
A
Ishida
M
M
Gambello
M J
MJ
Yingling
J
J
Wynshaw-Boris
A
A
Hirotsune
S
S
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D001233:Aspergillus nidulans; D001370:Axonal Transport / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics* / Q000378:metabolism*; D002465:Cell Movement; D002478:Cells, Cultured; D018385:Centrosome / Q000378:metabolism; D051360:Cyclin-Dependent Kinase 5; D018844:Cyclin-Dependent Kinases / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D004398:Dyneins / Q000378:metabolism*; D005656:Fungal Proteins / Q000235:genetics; D006801:Humans; D046911:Macromolecular Substances; D051379:Mice; D008817:Mice, Mutant Strains; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D008969:Molecular Sequence Data; D009420:Nervous System / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D010766:Phosphorylation; D021122:Protein Subunits; D017386:Sequence Homology, Amino Acid; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D020798:Two-Hybrid System Techniques
D002352:Carrier Proteins; D005656:Fungal Proteins; D046911:Macromolecular Substances; D008869:Microtubule-Associated Proteins; C421108:NDEL1 protein, human; C486015:Ndel1 protein, mouse; D021122:Protein Subunits; C121041:RO-11 protein, Neurospora crassa; D051360:Cyclin-Dependent Kinase 5; C495905:CDK5 protein, human; C495906:Cdk5 protein, mouse; D018844:Cyclin-Dependent Kinases; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; C513190:Pafah1b1 protein, mouse; D004398:Dyneins