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Regulation of cytoplasmic dynein behaviour and microtubule organization by mammalian Lis1

Abstract

Whereas total loss of Lis1 is lethal, disruption of one allele of the Lis1 gene results in brain abnormalities, indicating that developing neurons are particularly sensitive to a reduction in Lis1 dosage. Here we show that Lis1 is enriched in neurons relative to levels in other cell types, and that Lis1 interacts with the microtubule motor cytoplasmic dynein. Production of more Lis1 in non-neuronal cells increases retrograde movement of cytoplasmic dynein and leads to peripheral accumulation of microtubules. These changes may reflect neuron-like dynein behaviours induced by abundant Lis1. Lis1 deficiency produces the opposite phenotype. Our results indicate that abundance of Lis1 in neurons may stimulate specific dynein functions that function in neuronal migration and axon growth.

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Figure 1: Distribution of Lis1 in neurons and non-neuronal cells.
Figure 2: Lis1 and dynein IC co-localize in neurons and Cos-7 cells.
Figure 3: Lis1 interacts with p150glued and dynein IC in the brain.
Figure 4: Overexpression of Lis1 in Cos-7 cells.
Figure 5: Lis1 affects the subcellular distribution of dynein–dynactin.
Figure 6: Overexpression of Lis1 affects microtubule distribution.
Figure 7: Loss of Lis1 function stimulates dispersal of p150glued and perinuclear microtubule enrichment.
Figure 8: Levels of Lis1 affect the distribution of the Golgi complex.
Figure 9: Model for regulation of cytoplasmic dynein by Lis1.

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Acknowledgements

We thank L. Luo for sharing results before publication, and members of the Tsai laboratory for evaluation of the work and the manuscript. Correspondence and requests for materials should be addressed to L.H.T. Supplementary Information is available on our website or as paper copy from the London editorial office of Nature Cell Biology.

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Correspondence to Li-Huei Tsai.

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Figure S1

Lis1 induces juxtanuclear accumulation of dynein IC, p150gluedand Golgi membranes, and peripheral accumulation of microtubules in the same cells. (PDF 215 kb)

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Smith, D., Niethammer, M., Ayala, R. et al. Regulation of cytoplasmic dynein behaviour and microtubule organization by mammalian Lis1. Nat Cell Biol 2, 767–775 (2000). https://doi.org/10.1038/35041000

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