title: Dynein light chain 1 and a spindle-associated adaptor promote dynein asymmetry and spindle orientation.
abstract: The cytoplasmic dynein motor generates pulling forces to center and orient the mitotic spindle within the cell. During this positioning process, dynein oscillates from one pole of the cell cortex to the other but only accumulates at the pole farthest from the spindle. Here, we show that dynein light chain 1 (DYNLL1) is required for this asymmetric cortical localization of dynein and has a specific function defining spindle orientation. DYNLL1 interacted with a spindle-microtubule-associated adaptor formed by CHICA and HMMR via TQT motifs in CHICA. In cells depleted of CHICA or HMMR, the mitotic spindle failed to orient correctly in relation to the growth surface. Furthermore, CHICA TQT motif mutants localized to the mitotic spindle but failed to recruit DYNLL1 to spindle microtubules and did not correct the spindle orientation or dynein localization defects. These findings support a model where DYNLL1 and CHICA-HMMR form part of the regulatory system feeding back spindle position to dynein at the cell cortex.
authors.affiliation: Department of Biochemistry, University of Oxford, Oxford OX1 3QU, England, UK.
authors.forename: Anja K
authors.initials: AK
authors.lastname: Dunsch
authors.forename: Dean
authors.initials: D
authors.lastname: Hammond
authors.forename: Jennifer
authors.initials: J
authors.lastname: Lloyd
authors.forename: Lothar
authors.initials: L
authors.lastname: Schermelleh
authors.forename: Ulrike
authors.initials: U
authors.lastname: Gruneberg
authors.forename: Francis A
authors.initials: FA
authors.lastname: Barr
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D056445:Cytoplasmic Dyneins / Q000235:genetics* / Q000378:metabolism*; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006367:HeLa Cells; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism*; D008938:Mitosis / Q000235:genetics / Q000502:physiology; D009949:Orientation / Q000502:physiology; D008941:Spindle Apparatus / Q000235:genetics* / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D016326:Extracellular Matrix Proteins; C530359:FAM83D protein, human; D018960:Hyaluronan Receptors; D008869:Microtubule-Associated Proteins; C098946:hyaluronan-mediated motility receptor; C427758:DYNLL1 protein, human; D056445:Cytoplasmic Dyneins