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Integrin binding and mechanical tension induce movement of mRNA and ribosomes to focal adhesions

Nature volume 392, pages 730–733 (1998)Cite this article

Abstract

The extracellular matrix (ECM) activates signalling pathways that control cell behaviour by binding to cell-surface integrin receptors and inducing the formation of focal adhesion complexes (FACs)1,2. In addition to clustered integrins, FACs contain proteins that mechanically couple the integrins to the cytoskeleton3 and to immobilized signal-transducing molecules1,2. Cell adhesion to the ECM also induces a rapid increase in the translation of pre-existing messenger RNAs4,5. Gene expression can be controlled locally by targeting mRNAs to specialized cytoskeletal domains6. Here we investigate whether cell binding to the ECM promotes formation of a cytoskeletal microcompartment specialized for translational control at the site of integrin binding. High-resolution in situ hybridization revealed that mRNA and ribosomes rapidly and specifically localized to FACs that form when cells bind to ECM-coated microbeads. Relocation of these protein synthesis components to the FAC depended on the ability of integrins to mechanically couple the ECM to the contractile cytoskeleton and on associated tension-moulding of the actin lattice. Our results suggest a new type of gene regulation by integrins and by mechanical stress which may involve translation of mRNAs into proteins near the sites of signal reception.

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Figure 1: Recruitment of mRNA and ribosomes to FACs 20 min after cell binding to ECM-coated microbeads.
Figure 2: Integrin-dependent relocalization of poly(A)+ RNA and ribosomes to the FAC at 20 min after bead binding.
Figure 3: Kinetics of mRNA and ribosome recruitment to the FAC.
Figure 4: The role of the CSK and mechanical tension in the recruitment process.

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Acknowledgements

We thank K. Taneja, S. Shenoy, N. Wang, J. Fredberg, S. Kourembanas, G. Lee, G.Whitesides and the Biomedical Imaging Facility at the University of Massachusetts in Worcester for key reagents, equipment and technical expertise, and B. Peters and C. Chen for discussion. This work was supported by grants from the NIH and NASA and an American Cancer Society postdoctoral fellowship.

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Authors and Affiliations

  1. Departments of Surgery and Pathology, Children's Hospital and Harvard Medical School, 300 Longwood Avenue, Boston, 02115, Massachusetts, USA

    Marina E. Chicurel, Christian J. Meyer & Donald E. Ingber

  2. Department of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva University, Bronx, 10461, New York, USA

    Marina E. Chicurel & Robert H. Singer

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  1. Marina E. Chicurel
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Correspondence to Donald E. Ingber.

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Chicurel, M., Singer, R., Meyer, C. et al. Integrin binding and mechanical tension induce movement of mRNA and ribosomes to focal adhesions. Nature 392, 730–733 (1998). https://doi.org/10.1038/33719

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