title: Release from myosin V via regulated recruitment of an E3 ubiquitin ligase controls organelle localization.
abstract: Molecular motors transport organelles to specific subcellular locations. Upon arrival at their correct locations, motors release organelles via unknown mechanisms. The yeast myosin V, Myo2, binds the vacuole-specific adaptor Vac17 to transport the vacuole from the mother cell to the bud. Here, we show that vacuole detachment from Myo2 occurs in multiple regulated steps along the entire pathway of vacuole transport. Detachment initiates in the mother cell with the phosphorylation of Vac17 that recruits the E3 ligase Dma1 to the vacuole. However, Dma1 recruitment also requires the assembly of the vacuole transport complex and is first observed after the vacuole enters the bud. Dma1 remains on the vacuole until the bud and mother vacuoles separate. Subsequently, Dma1 targets Vac17 for proteasomal degradation. Notably, we find that the termination of peroxisome transport also requires Dma1. We predict that this is a general mechanism that detaches myosin V from select cargoes.
authors.affiliation: Program in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Richard G
authors.initials: RG
authors.lastname: Yau
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Yutian
authors.initials: Y
authors.lastname: Peng
authors.affiliation: Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA.
authors.forename: Rajeshwari R
authors.initials: RR
authors.lastname: Valiathan
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Shanda R
authors.initials: SR
authors.lastname: Birkeland
authors.affiliation: Program in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Department of Human Genetics, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Wilson
authors.affiliation: Program in Cell and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA; Life Sciences Institute, University of Michigan, Ann Arbor, MI 48109, USA; Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA. Electronic address: lweisman@umich.edu.
authors.forename: Lois S
authors.initials: LS
authors.lastname: Weisman
mesh_terms: D000595:Amino Acid Sequence; D001692:Biological Transport; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D008969:Molecular Sequence Data; D018995:Myosin Heavy Chains / Q000378:metabolism*; D024701:Myosin Type V / Q000378:metabolism*; D015388:Organelles / Q000378:metabolism*; D020675:Peroxisomes / Q000378:metabolism*; D010766:Phosphorylation; D011956:Receptors, Cell Surface / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D014617:Vacuoles / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; C493793:DMA2 protein, S cerevisiae; C493792:Dma1 protein, S cerevisiae; C077512:MYO2 protein, S cerevisiae; D011956:Receptors, Cell Surface; D029701:Saccharomyces cerevisiae Proteins; C472499:VAC17 protein, S cerevisiae; D033921:Vesicular Transport Proteins; D024701:Myosin Type V; D018995:Myosin Heavy Chains