Dynactin function in mitotic spindle positioning

Traffic. 2008 Apr;9(4):510-27. doi: 10.1111/j.1600-0854.2008.00710.x. Epub 2008 Jan 22.

Abstract

Dynactin is a multisubunit protein complex necessary for dynein function. Here, we investigated the function of dynactin in budding yeast. Loss of dynactin impaired movement and positioning of the mitotic spindle, similar to loss of dynein. Dynactin subunits required for function included p150(Glued), dynamitin, actin-related protein (Arp) 1 and p24. Arp10 and capping protein were dispensable, even in combination. All dynactin subunits tested localized to dynamic plus ends of cytoplasmic microtubules, to stationary foci on the cell cortex and to spindle pole bodies. The number of molecules of dynactin in those locations was small, less than five. In the absence of dynactin, dynein accumulated at plus ends and did not appear at the cell cortex, consistent with a role for dynactin in offloading dynein from the plus end to the cortex. Dynein at the plus end was necessary for dynactin plus-end targeting. p150(Glued) was the only dynactin subunit sufficient for plus-end targeting. Interactions among the subunits support a molecular model that resembles the current model for brain dynactin in many respects; however, three subunits at the pointed end of brain dynactin appear to be absent from yeast.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cytoskeletal Proteins / genetics
  • Cytoskeletal Proteins / metabolism
  • Dynactin Complex
  • Dyneins / metabolism
  • Microtubule-Associated Proteins / genetics
  • Microtubule-Associated Proteins / metabolism*
  • Microtubules / metabolism
  • Microtubules / ultrastructure
  • Protein Subunits / genetics
  • Protein Subunits / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Spindle Apparatus / metabolism*
  • Spindle Apparatus / ultrastructure

Substances

  • ARP1 protein, S cerevisiae
  • Cytoskeletal Proteins
  • Dynactin Complex
  • Microtubule-Associated Proteins
  • NIP100 protein, S cerevisiae
  • Protein Subunits
  • Recombinant Fusion Proteins
  • Saccharomyces cerevisiae Proteins
  • Dyneins