A LIS1/NUDEL/Cytoplasmic Dynein Heavy Chain Complex in the Developing and Adult Nervous System
Copyright policy )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.
- University of California, San Diego United States
Centrosome, Cytoplasm, Macromolecular Substances, Neuroscience(all), Molecular Sequence Data, Dyneins, Cyclin-Dependent Kinase 5, Axonal Transport, Microtubules, Aspergillus nidulans, Cyclin-Dependent Kinases, Mice, Mutant Strains, Fungal Proteins, Mice, Cell Movement, 1-Alkyl-2-acetylglycerophosphocholine Esterase, Animals, Humans, Carrier Proteins, Microtubule-Associated Proteins, Cells, Cultured
Centrosome, Cytoplasm, Macromolecular Substances, Neuroscience(all), Molecular Sequence Data, Dyneins, Cyclin-Dependent Kinase 5, Axonal Transport, Microtubules, Aspergillus nidulans, Cyclin-Dependent Kinases, Mice, Mutant Strains, Fungal Proteins, Mice, Cell Movement, 1-Alkyl-2-acetylglycerophosphocholine Esterase, Animals, Humans, Carrier Proteins, Microtubule-Associated Proteins, Cells, Cultured
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