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J Cell Sci. 2019 Jan 16;132(2). pii: jcs226704. doi: 10.1242/jcs.226704.

Contractility kits promote assembly of the mechanoresponsive cytoskeletal network.

Author information

1
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2
Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
3
Department of Biophysics and Biophysical Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
4
Department of Medicine, The Smidt Heart Institute and Advanced Clinical Biosystems Institute, Cedar-Sinai Medical Center, Los Angeles, CA 90048, USA.
5
Department of Biophysics, Johns Hopkins University, Baltimore, MD 21218, USA.
6
Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA.
7
Howard Hughes Medical Institute, Baltimore, MD 21205, USA.
8
Department of Cell Biology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA dnr@jhmi.edu.
9
Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
10
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

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.This article has an associated First Person interview with the first author of the paper.

KEYWORDS:

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

PMID:
30559246
PMCID:
PMC6362397
[Available on 2020-01-15]
DOI:
10.1242/jcs.226704

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