title: Dynein light intermediate chains maintain spindle bipolarity by functioning in centriole cohesion.
abstract: Cytoplasmic dynein 1 (dynein) is a minus end-directed microtubule motor protein with many cellular functions, including during cell division. The role of the light intermediate chains (LICs; DYNC1LI1 and 2) within the complex is poorly understood. In this paper, we have used small interfering RNAs or morpholino oligonucleotides to deplete the LICs in human cell lines and Xenopus laevis early embryos to dissect the LICs' role in cell division. We show that although dynein lacking LICs drives microtubule gliding at normal rates, the LICs are required for the formation and maintenance of a bipolar spindle. Multipolar spindles with poles that contain single centrioles were formed in cells lacking LICs, indicating that they are needed for maintaining centrosome integrity. The formation of multipolar spindles via centrosome splitting after LIC depletion could be rescued by inhibiting Eg5. This suggests a novel role for the dynein complex, counteracted by Eg5, in the maintenance of centriole cohesion during mitosis.
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK.
authors.forename: Laura A
authors.initials: LA
authors.lastname: Jones
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK.
authors.forename: Cécile
authors.initials: C
authors.lastname: Villemant
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK.
authors.forename: Toby
authors.initials: T
authors.lastname: Starborg
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Salter
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK.
authors.forename: Georgina
authors.initials: G
authors.lastname: Goddard
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK.
authors.forename: Peter
authors.initials: P
authors.lastname: Ruane
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Woodman
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK.
authors.forename: Nancy
authors.initials: N
authors.lastname: Papalopulu
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK viki.allan@manchester.ac.uk sarah.woolner@manchester.ac.uk.
authors.forename: Sarah
authors.initials: S
authors.lastname: Woolner
authors.affiliation: Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, England, UK viki.allan@manchester.ac.uk sarah.woolner@manchester.ac.uk.
authors.forename: Victoria J
authors.initials: VJ
authors.lastname: Allan
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement; D002502:Centrioles / Q000502:physiology; D056445:Cytoplasmic Dyneins / Q000235:genetics / Q000378:metabolism*; D000072159:Dynactin Complex; D005260:Female; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors*; D018386:Kinetochores; D008868:Microtubule Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology*; D008969:Molecular Sequence Data; D034622:RNA Interference; D034741:RNA, Small Interfering; D008941:Spindle Apparatus / Q000235:genetics / Q000473:pathology*; D014982:Xenopus laevis
chemical_list: D000072159:Dynactin Complex; C470243:KIF11 protein, human; D008868:Microtubule Proteins; D008869:Microtubule-Associated Proteins; D034741:RNA, Small Interfering; C424131:DYNC1LI1 protein, human; D056445:Cytoplasmic Dyneins; C548808:DYNC1LI2 protein, human; D016547:Kinesins