LIS1 and NudE induce a persistent dynein force-producing state

Richard Mckenney, Michael Vershinin, Ambarish Kunwar, Richard B. Vallee, Steven P. Gross

Research output: Contribution to journalArticle

248 Scopus citations

Abstract

Cytoplasmic dynein is responsible for many aspects of cellular and subcellular movement. LIS1, NudE, and NudEL are dynein interactors initially implicated in brain developmental disease but now known to be required in cell migration, nuclear, centrosomal, and microtubule transport, mitosis, and growth cone motility. Identification of a specific role for these proteins in cytoplasmic dynein motor regulation has remained elusive. We find that NudE stably recruits LIS1 to the dynein holoenzyme molecule, where LIS1 interacts with the motor domain during the prepowerstroke state of the dynein crossbridge cycle. NudE abrogates dynein force production, whereas LIS1 alone or with NudE induces a persistent-force dynein state that improves ensemble function of multiple dyneins for transport under high-load conditions. These results likely explain the requirement for LIS1 and NudE in the transport of nuclei, centrosomes, chromosomes, and the microtubule cytoskeleton as well as the particular sensitivity of migrating neurons to reduced LIS1 expression.

Original languageEnglish (US)
Pages (from-to)304-314
Number of pages11
JournalCell
Volume141
Issue number2
DOIs
StatePublished - Apr 1 2010
Externally publishedYes

Keywords

  • Cellbio
  • Molneuro

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Mckenney, R., Vershinin, M., Kunwar, A., Vallee, R. B., & Gross, S. P. (2010). LIS1 and NudE induce a persistent dynein force-producing state. Cell, 141(2), 304-314. https://doi.org/10.1016/j.cell.2010.02.035