Dynein is regulated by the stability of its microtubule track

J Cell Biol. 2017 Jul 3;216(7):2047-2058. doi: 10.1083/jcb.201611105. Epub 2017 Jun 1.

Abstract

How dynein motors accurately move cargoes is an important question. In budding yeast, dynein moves the mitotic spindle to the predetermined site of cytokinesis by pulling on astral microtubules. In this study, using high-resolution imaging in living cells, we discover that spindle movement is regulated by changes in microtubule plus-end dynamics that occur when dynein generates force. Mutants that increase plus-end stability increase the frequency and duration of spindle movements, causing positioning errors. We find that dynein plays a primary role in regulating microtubule dynamics by destabilizing microtubules. In contrast, the dynactin complex counteracts dynein and stabilizes microtubules through a mechanism involving the shoulder subcomplex and the cytoskeletal-associated protein glycine-rich domain of Nip100/p150glued Our results support a model in which dynein destabilizes its microtubule substrate by using its motility to deplete dynactin from the plus end. We propose that interplay among dynein, dynactin, and the stability of the microtubule substrate creates a mechanism that regulates accurate spindle positioning.

Publication types

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

MeSH terms

  • Cell Cycle*
  • Dynactin Complex / genetics
  • Dynactin Complex / metabolism
  • Dyneins / genetics
  • Dyneins / metabolism*
  • Microtubules / metabolism*
  • Mutation
  • Protein Stability
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Spindle Apparatus / metabolism*
  • Time Factors

Substances

  • Dynactin Complex
  • NIP100 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • DYN1 protein, S cerevisiae
  • Dyneins