Contractility kits promote assembly of the mechanoresponsive cytoskeletal network
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. Further, 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) poised to integrate into the cortex upon diffusional encounter coincident with mechanical inputs.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Jan 01, 2018
- Source ID
- 10.1242/jcs.226704
Entities
People
- Douglas N. Robinson
- Irina Tchernyshyov
- Jennifer E Van Eyk
- Priyanka Kothari
- Taekjip Ha
- Vasudha Aggarwal
- Vasudha Srivastava
Organizations
- Defense Advanced Research Projects Agency
- Howard Hughes Medical Institute
- Johns Hopkins University
- National Institutes of Health
- Office of Extramural Research