Title

A role for the lissencephaly gene LIS1 in mitosis and cytoplasmic dynein function

GSBS Program

Biochemistry & Molecular Pharmacology

UMMS Affiliation

Graduate School of Biomedical Sciences; Department of Physiology; Department of Cell Biology

Date

11-1-2000

Document Type

Article

Medical Subject Headings

1-Alkyl-2-acetylglycerophosphocholine Esterase; Animals; COS Cells; Cell Division; Cell Line; Cercopithecus aethiops; Cytoplasm; Dogs; Dynein ATPase; Gene Expression; Humans; Kinetochores; Microtubule-Associated Proteins; Microtubules; Mitosis; Precipitin Tests; Subcellular Fractions

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: Nat Cell Biol. 2000 Nov;2(11):784-91. Link to article on publisher's site

Related Resources

Link to article in PubMed