A role for the lissencephaly gene LIS1 in mitosis and cytoplasmic dynein function.
Mutations in the LIS1 gene cause gross histological disorganization of the developing human brain, resulting in a brain surface that is almost smooth. Here we show that LIS1 protein co-immunoprecipitates with cytoplasmic dynein and dynactin, and localizes to the cell cortex and to mitotic kinetochores, which are known sites for binding of cytoplasmic dynein. Overexpression of LIS1 in cultured mammalian cells interferes with mitotic progression and leads to spindle misorientation. Injection of anti-LIS1 antibody interferes with attachment of chromosomes to the metaphase plate, and leads to chromosome loss. We conclude that LIS1 participates in a subset of dynein functions, and may regulate the division of neuronal progenitor cells in the developing brain.
Faulkner
N E
NE
Department of Cell Biology University of Massachusetts Medical School, 377 Plantation Street, Worcester, Massachusetts 01605, USA.
Dujardin
D L
DL
Tai
C Y
CY
Vaughan
K T
KT
O'Connell
C B
CB
Wang
Y
Y
Vallee
R B
RB
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000818:Animals; D019556:COS Cells; D002455:Cell Division; D002460:Cell Line; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D004285:Dogs; D000072159:Dynactin Complex; D004398:Dyneins / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D011233:Precipitin Tests / Q000379:methods; D013347:Subcellular Fractions
D000072159:Dynactin Complex; D008869:Microtubule-Associated Proteins; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; C084102:PAFAH1B1 protein, human; D004398:Dyneins