Integrin binding and mechanical tension induce movement of mRNA and ribosomes to focal adhesions.
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). In addition to clustered integrins, FACs contain proteins that mechanically couple the integrins to the cytoskeleton and to immobilized signal-transducing molecules. Cell adhesion to the ECM also induces a rapid increase in the translation of preexisting messenger RNAs. Gene expression can be controlled locally by targeting mRNAs to specialized cytoskeletal domains. 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.
Chicurel
M E
ME
Department of Surgery, Children's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA.
Singer
R H
RH
Meyer
C J
CJ
Ingber
D E
DE
D016475:3T3 Cells; D000818:Animals; D002417:Cattle; D002451:Cell Compartmentation; D002478:Cells, Cultured; D005109:Extracellular Matrix / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D016023:Integrins / Q000378:metabolism*; D007700:Kinetics; D051379:Mice; D011061:Poly A; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000502:physiology; D012270:Ribosomes / Q000502:physiology*; D013314:Stress, Mechanical
D016023:Integrins; D012333:RNA, Messenger; D011061:Poly A