Contractility kits promote assembly of the mechanoresponsive cytoskeletal network

Priyanka Kothari, Vasudha Srivastava, Vasudha Aggarwal, Irina Tchernyshyov, Jennifer E. Van Eyk, Taekjip Ha, Douglas Robinson

Research output: Contribution to journalArticle

Abstract

Cellular contractility is governed by a control system of proteins that integrates internal and external cues to drive diverse shape change processes. This contractility controller includes myosin II motors, actin crosslinkers and protein scaffolds, which exhibit robust and cooperative mechanoaccumulation. However, the biochemical interactions and feedback mechanisms that drive the controller remain unknown. Here, we use a proteomics approach to identify direct interactors of two key nodes of the contractility controller in the social amoeba Dictyostelium discoideum: the actin crosslinker cortexillin I and the scaffolding protein IQGAP2. We highlight several unexpected proteins that suggest feedback from metabolic and RNA-binding proteins on the contractility controller. Quantitative in vivo biochemical measurements reveal direct interactions between myosin II and cortexillin I, which form the core mechanosensor. Furthermore, IQGAP1 negatively regulates mechanoresponsiveness by competing with IQGAP2 for binding the myosin II–cortexillin I complex. These myosin II–cortexillin I–IQGAP2 complexes are pre-assembled into higher-order mechanoresponsive contractility kits (MCKs) that are poised to integrate into the cortex upon diffusional encounter coincident with mechanical inputs.

Original languageEnglish (US)
Article numberjcs226704
JournalJournal of Cell Science
Volume132
Issue number2
DOIs
StatePublished - Jan 1 2019

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Keywords

  • Cortexillin I
  • FCCS
  • IQGAP
  • LC-MS
  • Myosin II
  • SiMPull

ASJC Scopus subject areas

  • Cell Biology

Cite this

Kothari, P., Srivastava, V., Aggarwal, V., Tchernyshyov, I., Van Eyk, J. E., Ha, T., & Robinson, D. (2019). Contractility kits promote assembly of the mechanoresponsive cytoskeletal network. Journal of Cell Science, 132(2), [jcs226704]. https://doi.org/10.1242/jcs.226704