title: Neural Wiskott-Aldrich syndrome protein is required for accurate chromosome congression and segregation.
abstract: The accurate distribution and segregation of replicated chromosomes through mitosis is crucial for cellular viability and development of organisms. Kinetochores are responsible for the proper congression and segregation of chromosomes. Here, we show that neural Wiskott-Aldrich syndrome protein (N-WASP) localizes to and forms a complex with kinetochores in mitotic cells. Depletion of NWASP by RNA interference causes chromosome misalignment, prolonged mitosis, and abnormal chromosomal segregation, which is associated with decreased proliferation of N-WASP-deficient cells. N-WASP-deficient cells display defects in the kinetochores recruitment of inner and outer kinetochore components, CENP-A, CENP-E, and Mad2. Live-cell imaging analysis of GFP-α-tubulin revealed that depletion of N-WASP impairs microtubule attachment to chromosomes in mitotic cells. All these results indicate that N-WASP plays a role in efficient assembly of kinetochores and attachment of microtubules to chromosomes, which is essential for accurate chromosome congression and segregation.
authors.affiliation: Department of Chemistry, Pukyong National University, Busan, 608-737, Korea. parksj@pknu.ac.kr
authors.forename: Sun Joo
authors.initials: SJ
authors.lastname: Park
authors.forename: Tadaomi
authors.initials: T
authors.lastname: Takenawa
mesh_terms: D001324:Autoantigens / Q000378:metabolism; D053144:Cell Nucleus Shape / Q000235:genetics; D049109:Cell Proliferation; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D020090:Chromosome Segregation; D002875:Chromosomes / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D018386:Kinetochores / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D015739:Nocodazole / Q000494:pharmacology; D011485:Protein Binding; D034622:RNA Interference; D014404:Tubulin / Q000378:metabolism; D050257:Tubulin Modulators / Q000494:pharmacology; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal / Q000235:genetics / Q000378:metabolism*
chemical_list: D001324:Autoantigens; C000619700:CENPA protein, human; D000076247:Centromere Protein A; D002868:Chromosomal Proteins, Non-Histone; D014404:Tubulin; D050257:Tubulin Modulators; D051317:Wiskott-Aldrich Syndrome Protein, Neuronal; D015739:Nocodazole