@article{56e837b74c624b36807bd003277b5b61,
title = "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. 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.",
keywords = "Cortexillin I, FCCS, IQGAP, LC-MS, Myosin II, SiMPull",
author = "Priyanka Kothari and Vasudha Srivastava and Vasudha Aggarwal and Irina Tchernyshyov and {Van Eyk}, Jennifer and Taekjip Ha and Robinson, {Douglas N.}",
note = "Funding Information: We thank the members of the D.N.R. laboratory for helpful discussions. We thank Sheil Kee for generating the GFP-myosin II S1-mCherry construct. We also thank the Johns Hopkins University Microscope Facility, particularly Barbara Smith and Hoku West-Foyle, for providing equipment and technical assistance for FCCS experiments. This work was supported by the National Institutes of Health (R01GM66817 to D.N.R., R21AG042332 to T.H., F31GM122258 to P.K., T32GM007445 to the BCMB Graduate Program, S10 OD016374 to the JHU Microscope Facility); the Defense Advanced Research Projects Agency (HR0011-16-C-0139 to D.N.R.); the Erika J. Glazer chair in Women{\textquoteright}s Heart Health (J.E.V.E.); the Barbra Streisand Women{\textquoteright}s Heart Center (J.E.V.E.); and the Advanced Clinical Biosystems Institute (J.E.V.E.). T.H. is an investigator with the Howard Hughes Medical Institute. Deposited in PMC for release after 12 months. Funding Information: This work was supported by the National Institutes of Health (R01GM66817 to D.N.R., R21AG042332 to T.H., F31GM122258 to P.K., T32GM007445 to the BCMB Graduate Program, S10 OD016374 to the JHU Microscope Facility); the Defense Advanced Research Projects Agency (HR0011-16-C-0139 to D.N.R.); the Erika J. Glazer chair in Women{\textquoteright}s Heart Health (J.E.V.E.); the Barbra Streisand Women{\textquoteright}s Heart Center (J.E.V.E.); and the Advanced Clinical Biosystems Institute (J.E.V.E.). T.H. is an investigator with the Howard Hughes Medical Institute. Deposited in PMC for release after 12 months. Publisher Copyright: {\textcopyright} 2019. Published by The Company of Biologists Ltd.",
year = "2019",
month = jan,
day = "1",
doi = "10.1242/jcs.226704",
language = "English (US)",
volume = "132",
journal = "Journal of cell science",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "2",
}