title: Motor- and tail-dependent targeting of dynein to microtubule plus ends and the cell cortex.
abstract: BACKGROUND
  Cytoplasmic dynein mediates spindle positioning in budding yeast by powering sliding of microtubules along the cell cortex. Although previous studies have demonstrated cortical and plus-end targeting of dynein heavy chain (Dyn1/HC), the regulation of its recruitment to these sites remains elusive.
  
  
  RESULTS
  Here we show that separate domains of Dyn1/HC confer differential localization to the dynein complex. The N-terminal tail domain targets Dyn1/HC to cortical Num1 receptor sites, whereas the C-terminal motor domain targets Dyn1/HC to microtubule plus ends in a Bik1/CLIP-170- and Pac1/LIS1-dependent manner. Surprisingly, the isolated motor domain blocks plus-end targeting of Dyn1/HC, leading to a dominant-negative effect on dynein function. Overexpression of Pac1/LIS1, but not Bik1/CLIP-170, rescues the dominant negativity by restoring Dyn1/HC to plus ends. In contrast, the isolated tail domain has no inhibitory effect on Dyn1/HC targeting and function. However, cortical targeting of the tail construct is more robust than full-length Dyn1/HC and occurs independently of Bik1/CLIP-170 or Pac1/LIS1.
  
  
  CONCLUSIONS
  Our results suggest that the cortical association domain is normally masked in the full-length dynein molecule. We propose that targeting of dynein to plus ends unmasks the tail, priming the motor for off-loading to cortical Num1 sites.
authors.affiliation: Biology Department, University of Massachusetts at Amherst, Amherst, MA 01003, USA.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Markus
authors.forename: Jesse J
authors.initials: JJ
authors.lastname: Punch
authors.forename: Wei-Lih
authors.initials: WL
authors.lastname: Lee
mesh_terms: D004398:Dyneins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008954:Models, Biological; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D004718:Saccharomycetales; D008941:Spindle Apparatus / Q000378:metabolism*
chemical_list: D004398:Dyneins