A force-sensitive mutation reveals a non-canonical role for dynein in anaphase progression

  • David Salvador-Garcia
  • , Li Jin
  • , Andrew Hensley
  • , Mert Gölcük
  • , Emmanuel Gallaud
  • , Sami Chaaban
  • , Fillip Port
  • , Alessio Vagnoni
  • , Vicente José Planelles-Herrero
  • , Mark A. McClintock
  • , Emmanuel Derivery
  • , Andrew P. Carter
  • , Régis Giet
  • , Mert Gür
  • , Ahmet Yildiz
  • , Simon L. Bullock*
  • *Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

The diverse roles of the dynein motor in shaping microtubule networks and cargo transport complicate in vivo analysis of its functions significantly. To address this issue, we have generated a series of missense mutations in Drosophila Dynein heavy chain. We show that mutations associated with human neurological disease cause a range of defects, including impaired cargo trafficking in neurons. We also describe a novel microtubule-binding domain mutation that specifically blocks the metaphase–anaphase transition during mitosis in the embryo. This effect is independent from dynein’s canonical role in silencing the spindle assembly checkpoint. Optical trapping of purified dynein complexes reveals that this mutation only compromises motor performance under load, a finding rationalized by the results of all-atom molecular dynamics simulations. We propose that dynein has a novel function in anaphase progression that depends on it operating in a specific load regime. More broadly, our work illustrates how in vivo functions of motors can be dissected by manipulating their mechanical properties.

Original languageEnglish
Article numbere202310022
JournalJournal of Cell Biology
Volume223
Issue number10
DOIs
Publication statusPublished - 7 Oct 2024

Bibliographical note

Publisher Copyright:
© 2024 MRC Laboratory of Molecular Biology.

Keywords

  • Biochemistry
  • Cell cycle and division
  • Cytoskeleton
  • Genetics

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