A role for the lissencephaly gene LIS1 in mitosis and cytoplasmic dynein function
A role for the lissencephaly gene LIS1 in mitosis and cytoplasmic dynein function
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DOI：
10.1038/35041020
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发表时间：
2000-11-01
影响因子：
21.3
通讯作者：
Vallee, RB
中科院分区：
文献类型：
--
作者：
Faulkner, NE;Dujardin, DL;Vallee, RB
LIS1基因的突变会导致发育中的人类大脑组织结构紊乱，导致大脑表面几乎光滑。在这里，我们表明，LIS1蛋白与细胞质动力蛋白和动力蛋白共免疫沉淀，并定位于细胞皮质和有丝分裂动粒，这是已知的网站结合细胞质动力蛋白。LIS1在培养的哺乳动物细胞中的过表达干扰有丝分裂进程并导致纺锤体错误取向。注射抗LIS1抗体干扰染色体附着到中期板，并导致染色体丢失。我们的结论是，LIS1参与了一个子集的动力蛋白功能，并可能调节神经元祖细胞在发育中的大脑分裂。
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.