Back to Search
Start Over
Dictyostelium LIS1 is a centrosomal protein required for microtubule/cell cortex interactions, nucleus/centrosome linkage, and actin dynamics.
- Source :
-
Molecular biology of the cell [Mol Biol Cell] 2005 Jun; Vol. 16 (6), pp. 2759-71. Date of Electronic Publication: 2005 Mar 30. - Publication Year :
- 2005
-
Abstract
- The widespread LIS1-proteins were originally identified as the target for sporadic mutations causing lissencephaly in humans. Dictyostelium LIS1 (DdLIS1) is a microtubule-associated protein exhibiting 53% identity to human LIS1. It colocalizes with dynein at isolated, microtubule-free centrosomes, suggesting that both are integral centrosomal components. Replacement of the DdLIS1 gene by the hypomorphic D327H allele or overexpression of an MBP-DdLIS1 fusion disrupted various dynein-associated functions. Microtubules lost contact with the cell cortex and were dragged behind an unusually motile centrosome. Previously, this phenotype was observed in cells overexpressing fragments of dynein or the XMAP215-homologue DdCP224. DdLIS1 was coprecipitated with DdCP224, suggesting that both act together in dynein-mediated cortical attachment of microtubules. Furthermore, DdLIS1-D327H mutants showed Golgi dispersal and reduced centrosome/nucleus association. Defects in DdLIS1 function also altered actin dynamics characterized by traveling waves of actin polymerization correlated with a reduced F-actin content. DdLIS1 could be involved in actin dynamics through Rho-GTPases, because DdLIS1 interacted directly with Rac1A in vitro. Our results show that DdLIS1 is required for maintenance of the microtubule cytoskeleton, Golgi apparatus and nucleus/centrosome association, and they suggest that LIS1-dependent alterations of actin dynamics could also contribute to defects in neuronal migration in lissencephaly patients.
- Subjects :
- Amino Acid Sequence
Animals
Cell Shape
Dictyostelium cytology
Gene Expression
Golgi Apparatus metabolism
Green Fluorescent Proteins metabolism
Microscopy, Fluorescence
Microtubule-Associated Proteins chemistry
Microtubule-Associated Proteins genetics
Molecular Sequence Data
Point Mutation
Protein Structure, Tertiary
Protozoan Proteins chemistry
Protozoan Proteins genetics
Sequence Homology, Amino Acid
Actins metabolism
Centrosome metabolism
Dictyostelium chemistry
Microtubule-Associated Proteins physiology
Microtubules metabolism
Protozoan Proteins physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1059-1524
- Volume :
- 16
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Molecular biology of the cell
- Publication Type :
- Academic Journal
- Accession number :
- 15800059
- Full Text :
- https://doi.org/10.1091/mbc.e05-01-0069