ArticleCurrent biology : CB2015
Rac1-dependent phosphorylation and focal adhesion recruitment of myosin IIA regulates migration and mechanosensing.
Article in Current biology : CB, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers.
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Who cites it
71 citing papers in PubMed, 115 citations in OpenAlex.
- A Wet-and-Dry Research Model: Unveiling Biomechanics in Odontoblast Polarization.International endodontic journal · 2026Article
- CD44 restricts EGFR mobility to polarize cytoskeletal signalling modules driving bleb-based migration.Nature cell biology · 2026Article
- Basigin (CD147) and calpain 4 (CapnS1) are partners in the generation of traction force but not in mechanosensing.The Journal of biological chemistry · 2026Article
- Effect of Load on Non-Muscle Myosin 2 Paralog Filaments in a Biomimetic Contractile Actin Array.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- Decoding Rho GTPase signalling networks in directed cell migration.Frontiers in cell and developmental biology · 2026Review
- Mouse scalp development requires Rac1 and SRF for the maintenance of mechanoresponsive mesenchyme.Development (Cambridge, England) · 2025Article
- Epigenetic regulatory protein chromobox family regulates multiple signalling pathways and mechanisms in cancer.Clinical epigenetics · 2025Review
- Article
- The mechanopathology of the tumor microenvironment: detection techniques, molecular mechanisms and therapeutic opportunities.Frontiers in cell and developmental biology · 2025Review
- Structure, regulation, and mechanisms of nonmuscle myosin-2.Cellular and molecular life sciences : CMLS · 2024Review
- Role of MARK2 in the nervous system and cancer.Cancer gene therapy · 2024Review
- Macrophage migration is differentially regulated by fibronectin and laminin through altered adhesion and myosin II localization.Molecular biology of the cell · 2024Article
- Arterial Mechanics, Extracellular Matrix, and Smooth Muscle Differentiation in Carotid Arteries Deficient for Rac1.Annals of vascular medicine and research · 2024Article
- Extracellular matrix sensing via modulation of orientational order of integrins and F-actin in focal adhesions.Life science alliance · 2023Article
- Key role for Rac in the early transcriptional response to extracellular matrix stiffness and stiffness-dependent repression of ATF3.Journal of cell science · 2023Article
- Article
- Self-Forming Norbornene-Tetrazine Hydrogels with Independently Tunable Properties.Macromolecular bioscience · 2023Article
- HBXIP blocks myosin-IIA assembly by phosphorylating and interacting with NMHC-IIA in breast cancer metastasis.Acta pharmaceutica Sinica. B · 2023Article
- Agent-based modeling predicts RAC1 is critical for ovarian cancer metastasis.Molecular biology of the cell · 2022Article
- Article
11 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
Abstract
backgroundCell migration requires coordinated formation of focal adhesions (FAs) and assembly and contraction of the actin cytoskeleton. Nonmuscle myosin II (MII) is a critical mediator of contractility and FA dynamics in cell migration. Signaling downstream of the small GTPase Rac1 also regulates FA and actin dynamics, but its role in regulation of MII during migration is less clear.
resultsWe found that Rac1 promotes association of MIIA with FA. Live-cell imaging showed that, whereas most MIIA at the leading edge assembled into dorsal contractile arcs, a substantial subset assembled in or was captured within maturing FA, and this behavior was promoted by active Rac1. Protein kinase C (PKC) activation was necessary and sufficient for integrin- and Rac1-dependent phosphorylation of MIIA heavy chain (HC) on serine1916 (S1916) and recruitment to FA. S1916 phosphorylation of MIIA HC and localization in FA was enhanced during cell spreading and ECM stiffness mechanosensing, suggesting upregulation of this pathway during physiological Rac1 activation. Phosphomimic and nonphosphorylatable MIIA HC mutants demonstrated that S1916 phosphorylation was necessary and sufficient for the capture and assembly of MIIA minifilaments in FA. S1916 phosphorylation was also sufficient to promote the rapid assembly of FAs to enhance cell migration and for the modulation of traction force, spreading, and migration by ECM stiffness.
conclusionsOur study reveals for the first time that Rac1 and integrin activation regulates MIIA HC phosphorylation through a PKC-dependent mechanism that promotes MIIA association with FAs and acts as a critical modulator of cell migration and mechanosensing.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.