Regulation of cytoplasmic dynein behaviour and microtubule organization by mammalian Lis1.
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.
Smith
D S
DS
Department of Pathology Harvard Medical School, 200 Longwood Avenue, Boston, Massachussetts 02115, USA.
Niethammer
M
M
Ayala
R
R
Zhou
Y
Y
Gambello
M J
MJ
Wynshaw-Boris
A
A
Tsai
L H
LH
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D019556:COS Cells; D002503:Centromere / Q000502:physiology; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism*; D005347:Fibroblasts / Q000166:cytology; D006056:Golgi Apparatus / Q000378:metabolism / Q000502:physiology; D007399:Interphase / Q000502:physiology; D007425:Intracellular Membranes / Q000378:metabolism / Q000502:physiology; D008322:Mammals; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000378:metabolism; D022101:Microtubule-Organizing Center / Q000378:metabolism / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D051381:Rats
D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D004398:Dyneins