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dc.contributor.authorPurohit, Aruna
dc.contributor.authorTynan, Sharon H.
dc.contributor.authorVallee, Richard B.
dc.contributor.authorDoxsey, Stephen J.
dc.date2022-08-11T08:10:05.000
dc.date.accessioned2022-08-23T16:54:53Z
dc.date.available2022-08-23T16:54:53Z
dc.date.issued1999-11-05
dc.date.submitted2008-08-15
dc.identifier.citationJ Cell Biol. 1999 Nov 1;147(3):481-92.
dc.identifier.issn0021-9525 (Print)
dc.identifier.pmid10545494
dc.identifier.urihttp://hdl.handle.net/20.500.14038/42599
dc.description.abstractPericentrin is a conserved protein of the centrosome involved in microtubule organization. To better understand pericentrin function, we overexpressed the protein in somatic cells and assayed for changes in the composition and function of mitotic spindles and spindle poles. Spindles in pericentrin-overexpressing cells were disorganized and mispositioned, and chromosomes were misaligned and missegregated during cell division, giving rise to aneuploid cells. We unexpectedly found that levels of the molecular motor cytoplasmic dynein were dramatically reduced at spindle poles. Cytoplasmic dynein was diminished at kinetochores also, and the dynein-mediated organization of the Golgi complex was disrupted. Dynein coimmunoprecipitated with overexpressed pericentrin, suggesting that the motor was sequestered in the cytoplasm and was prevented from associating with its cellular targets. Immunoprecipitation of endogenous pericentrin also pulled down cytoplasmic dynein in untransfected cells. To define the basis for this interaction, pericentrin was coexpressed with cytoplasmic dynein heavy (DHCs), intermediate (DICs), and light intermediate (LICs) chains, and the dynamitin and p150(Glued) subunits of dynactin. Only the LICs coimmunoprecipitated with pericentrin. These results provide the first physiological role for LIC, and they suggest that a pericentrin-dynein interaction in vivo contributes to the assembly, organization, and function of centrosomes and mitotic spindles.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=10545494&dopt=Abstract">Link to Article in PubMed</a>
dc.subjectAneuploidy
dc.subjectAnimals
dc.subjectAntigens
dc.subjectCOS Cells
dc.subjectCentrosome
dc.subjectChromosome Segregation
dc.subjectCytoplasm
dc.subjectDynein ATPase
dc.subjectFluorescent Antibody Technique
dc.subjectGolgi Apparatus
dc.subjectKinetochores
dc.subjectMice
dc.subjectMicrotubule-Associated Proteins
dc.subjectMitosis
dc.subjectMitotic Spindle Apparatus
dc.subjectMolecular Motor Proteins
dc.subjectMolecular Weight
dc.subjectPrecipitin Tests
dc.subjectProtein Binding
dc.subjectTransfection
dc.subjectCell Biology
dc.titleDirect interaction of pericentrin with cytoplasmic dynein light intermediate chain contributes to mitotic spindle organization
dc.typeJournal Article
dc.source.journaltitleThe Journal of cell biology
dc.source.volume147
dc.source.issue3
dc.identifier.legacyfulltexthttps://escholarship.umassmed.edu/cgi/viewcontent.cgi?article=1931&amp;context=oapubs&amp;unstamped=1
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/932
dc.identifier.contextkey579822
refterms.dateFOA2022-08-23T16:54:53Z
html.description.abstract<p>Pericentrin is a conserved protein of the centrosome involved in microtubule organization. To better understand pericentrin function, we overexpressed the protein in somatic cells and assayed for changes in the composition and function of mitotic spindles and spindle poles. Spindles in pericentrin-overexpressing cells were disorganized and mispositioned, and chromosomes were misaligned and missegregated during cell division, giving rise to aneuploid cells. We unexpectedly found that levels of the molecular motor cytoplasmic dynein were dramatically reduced at spindle poles. Cytoplasmic dynein was diminished at kinetochores also, and the dynein-mediated organization of the Golgi complex was disrupted. Dynein coimmunoprecipitated with overexpressed pericentrin, suggesting that the motor was sequestered in the cytoplasm and was prevented from associating with its cellular targets. Immunoprecipitation of endogenous pericentrin also pulled down cytoplasmic dynein in untransfected cells. To define the basis for this interaction, pericentrin was coexpressed with cytoplasmic dynein heavy (DHCs), intermediate (DICs), and light intermediate (LICs) chains, and the dynamitin and p150(Glued) subunits of dynactin. Only the LICs coimmunoprecipitated with pericentrin. These results provide the first physiological role for LIC, and they suggest that a pericentrin-dynein interaction in vivo contributes to the assembly, organization, and function of centrosomes and mitotic spindles.</p>
dc.identifier.submissionpathoapubs/932
dc.contributor.departmentDepartment of Cell Biology
dc.contributor.departmentProgram in Molecular Medicine
dc.source.pages481-92


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