title: The offloading model for dynein function: differential function of motor subunits.
abstract: During mitosis in budding yeast, dynein moves the mitotic spindle into the mother-bud neck. We have proposed an offloading model to explain how dynein works. Dynein is targeted to the dynamic plus end of a cytoplasmic microtubule, offloads to the cortex, becomes anchored and activated, and then pulls on the microtubule. Here, we perform functional studies of dynein intermediate chain (IC) and light intermediate chain (LIC). IC/Pac11 and LIC/Dyn3 are both essential for dynein function, similar to the heavy chain (HC/Dyn1). IC and LIC are targeted to the distal plus ends of dynamic cytoplasmic microtubules, as is HC, and their targeting depends on HC. Targeting of HC to the plus end depends on IC, but not LIC. IC also localizes as stationary dots at the cell cortex, the presumed result of offloading in our model, as does HC, but not LIC. Localization of HC to cortical dots depends on both IC and LIC. Thus, the IC and LIC accessory chains have different but essential roles in dynein function, providing new insight into the offloading model.
authors.affiliation: Department of Cell Biology and Physiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Wei-Lih
authors.initials: WL
authors.lastname: Lee
authors.forename: Michelle A
authors.initials: MA
authors.lastname: Kaiser
authors.forename: John A
authors.initials: JA
authors.lastname: Cooper
mesh_terms: D015153:Blotting, Western; D004398:Dyneins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D047468:Immunoprecipitation; D008856:Microscopy, Fluorescence; D008870:Microtubules / Q000378:metabolism; D008938:Mitosis / Q000502:physiology; D008954:Models, Biological; D020409:Molecular Motor Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D009154:Mutation; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D020409:Molecular Motor Proteins; D021122:Protein Subunits; D029701:Saccharomyces cerevisiae Proteins; C500511:DYN3 protein, S cerevisiae; C500512:intermediate chain 1 protein, S cerevisiae; D004398:Dyneins