Nudel/NudE and Lis1 promote dynein and dynactin interaction in the context of spindle morphogenesis

Shusheng Wang, Stephanie A. Ketcham, Arne Schön, Benjamin Goodman, Yueju Wang, John Yates, Ernesto Freire, Trina A. Schroer, Yixian Zheng

Research output: Contribution to journalArticle

Abstract

Lis1, Nudel/NudE, and dynactin are regulators of cytoplasmic dynein, a minus end-directed, microtubule (MT)-based motor required for proper spindle assembly and orientation. In vitro studies have shown that dynactin promotes processive movement of dynein on MTs, whereas Lis1 causes dynein to enter a persistent force-generating state (referred to here as dynein stall). Yet how the activities of Lis1, Nudel/NudE, and dynactin are coordinated to regulate dynein remains poorly understood in vivo. Working in Xenopus egg extracts, we show that Nudel/NudE facilitates the binding of Lis1 to dynein, which enhances the recruitment of dynactin to dynein. We further report a novel Lis1-dependent dynein-dynactin interaction that is essential for the organization of mitotic spindle poles. Finally, using assays for MT gliding and spindle assembly, we demonstrate an antagonistic relationship between Lis1 and dynactin that allows dynactin to relieve Lis1-induced dynein stall on MTs. Our findings suggest the interesting possibility that Lis1 and dynactin could alternately engage with dynein to allow the motor to promote spindle assembly.

Original languageEnglish (US)
Pages (from-to)3522-3533
Number of pages12
JournalMolecular biology of the cell
Volume24
Issue number22
DOIs
StatePublished - Nov 15 2013

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Wang, S., Ketcham, S. A., Schön, A., Goodman, B., Wang, Y., Yates, J., Freire, E., Schroer, T. A., & Zheng, Y. (2013). Nudel/NudE and Lis1 promote dynein and dynactin interaction in the context of spindle morphogenesis. Molecular biology of the cell, 24(22), 3522-3533. https://doi.org/10.1091/mbc.E13-05-0283