Integrin binding and mechanical tension induce movement of mRNA and ribosomes to focal adhesions
Integrin binding and mechanical tension induce movement of mRNA and ribosomes to focal adhesions
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DOI：
10.1038/33719
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发表时间：
1998-04-16
期刊：
影响因子：
64.8
通讯作者：
Ingber, DE
中科院分区：
文献类型：
--
作者：
Chicurel, ME;Singer, RH;Ingber, DE
细胞外基质（ECM）通过与细胞表面整合素受体结合并诱导粘着斑复合物（FACs）的形成，激活控制细胞行为的信号通路（1,2）。除了聚集的整合素外，粘着斑复合物还包含将整合素与细胞骨架机械耦合（3）以及与固定的信号转导分子耦合的蛋白质（1,2）。细胞与细胞外基质的粘附也会诱导预先存在的信使RNA的翻译迅速增加（4,5）。通过将mRNA靶向特定的细胞骨架区域可对基因表达进行局部控制（6）。在此我们研究细胞与细胞外基质的结合是否促进在整合素结合位点形成一个专门用于翻译控制的细胞骨架微区室。高分辨率原位杂交显示，当细胞与涂有细胞外基质的微珠结合时，mRNA和核糖体迅速且特异性地定位于形成的粘着斑复合物。这些蛋白质合成成分向粘着斑复合物的重新定位取决于整合素将细胞外基质与收缩性细胞骨架机械耦合的能力以及相关的肌动蛋白晶格的张力塑造。我们的研究结果表明整合素和机械应力可进行一种新型的基因调控，这可能涉及在信号接收位点附近将mRNA翻译成蛋白质。
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 cytoskeleton(3) and to immobilized signal-transducing molecules(1,2). Cell adhesion to the ECM also induces a rapid increase in the translation of preexisting messenger RNAs4,5. Gene expression can be controlled locally by targeting mRNAs to specialized cytoskeletal domains(6). 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.