PlumX Metrics
Embed PlumX Metrics

Conformational transitions of the mitotic adaptor Spindly underlie its interaction with Dynein and Dynactin

bioRxiv, ISSN: 2692-8205
2022
  • 4
    Citations
  • 0
    Usage
  • 0
    Captures
  • 0
    Mentions
  • 0
    Social Media
Metric Options:   Counts1 Year3 Year

Metrics Details

  • Citations
    4
    • Citation Indexes
      4
      • CrossRef
        4

Article Description

Cytoplasmic Dynein 1, or Dynein, is a microtubule minus-end directed motor. Dynein motility requires Dynactin and a family of activating adaptors that stabilize the Dynein-Dynactin complex and promote regulated interactions with cargo in space and time. How activating adaptors limit Dynein activation to specialized subcellular locales is unclear. Here, we reveal that Spindly, a mitotic Dynein adaptor at the kinetochore corona, exists natively in a closed conformation that occludes binding of Dynein-Dynactin to its CC1 box and Spindly motif. A structure-based analysis identified various mutations promoting an open conformation of Spindly that binds Dynein-Dynactin. A region of Spindly downstream from the Spindly motif and not required for cargo binding faces the CC1 box and stabilizes the intramolecular closed conformation. This region is also required for robust kinetochore localization of Spindly, suggesting that kinetochores promote Spindly activation to recruit Dynein. This mechanism may be paradigmatic for Dynein activation by other adaptors at various cellular locales.

Bibliographic Details

Ennio d'Amico; Verena Cmentowski; Franziska Müller; Sabine Wohlgemuth; Stefano Maffini; Ingrid R. Vetter; Andrea Musacchio; Misbha Ud Din Ahmad; Anastassis Perrakis; Mathias Girbig; Andrew P. Carter; Andreas Brockmeyer; Petra Janning

Cold Spring Harbor Laboratory

Biochemistry, Genetics and Molecular Biology; Agricultural and Biological Sciences; Immunology and Microbiology; Neuroscience; Pharmacology, Toxicology and Pharmaceutics

Provide Feedback

Have ideas for a new metric? Would you like to see something else here?Let us know