Muscle beta1D integrin reinforces the cytoskeleton-matrix link: modulation of integrin adhesive function by alternative splicing.
Muscle beta1D integrin reinforces the cytoskeleton-matrix link: modulation of integrin adhesive function by alternative splicing.
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DOI：
10.1083/jcb.139.6.1583
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发表时间：
1997-12-15
期刊：
影响因子：
--
通讯作者：
Tarone G
中科院分区：
文献类型：
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作者：
Belkin AM;Retta SF;Pletjushkina OY;Balzac F;Silengo L;Fassler R;Koteliansky VE;Burridge K;Tarone G
在CHO和GD 25中表达具有可变剪接胞质结构域的肌肉特异性β 1 D整合素，β1整合素阴性细胞导致其表型转化。与表达β 1A的细胞相比，β 1D转染的非肌细胞显示圆形形态，缺乏伪足活性，延迟扩散，减少迁移，并显著增强收缩力。转染的β1D靶向粘着斑，并有效地从细胞-基质接触部位置换内源性β1A和αvβ3整联蛋白。在几种类型的细胞外基质上观察到这种位移，并导致β1D转染子中粘着斑的稳定性提高。尽管细胞β1A整合素的显著部分可在毛地黄皂苷中提取，但大部分转染的β1D是毛地黄皂苷不溶性的，并且与去污剂不溶性细胞骨架强烈相关。β1D整合素与肌动蛋白细胞骨架的相互作用增强与其与talin的结合增强一致，并可能由其介导。相反，β1A与α-辅肌动蛋白的相互作用比β1D更强。β1D胞外域的由内而外驱动的激活增加了β1D转染子的配体结合和纤连蛋白基质组装。β1D整合素在非肌细胞中表达的表型效应是由于其与细胞骨架和细胞外配体的相互作用增强。它们平行于肌肉细胞在分化过程中经历的过渡。通过选择性剪接调节β1整联蛋白粘附功能是加强肌肉细胞中细胞骨架-基质连接的生理机制。这反映了β1D整合素在肌肉中的主要作用，其中收缩需要极其稳定的缔合。
Expression of muscle-specific β1D integrin with an alternatively spliced cytoplasmic domain in CHO and GD25, β1 integrin-minus cells leads to their phenotypic conversion. β1D-transfected nonmuscle cells display rounded morphology, lack of pseudopodial activity, retarded spreading, reduced migration, and significantly enhanced contractility compared with their β1A-expressing counterparts. The transfected β1D is targeted to focal adhesions and efficiently displaces the endogenous β1A and αvβ3 integrins from the sites of cell–matrix contact. This displacement is observed on several types of extracellular matrix substrata and leads to elevated stability of focal adhesions in β1D transfectants. Whereas a significant part of cellular β1A integrin is extractable in digitonin, the majority of the transfected β1D is digitonin-insoluble and is strongly associated with the detergent-insoluble cytoskeleton. Increased interaction of β1D integrin with the actin cytoskeleton is consistent with and might be mediated by its enhanced binding to talin. In contrast, β1A interacts more strongly with α-actinin, than β1D. Inside-out driven activation of the β1D ectodomain increases ligand binding and fibronectin matrix assembly by β1D transfectants. Phenotypic effects of β1D integrin expression in nonmuscle cells are due to its enhanced interactions with both cytoskeletal and extracellular ligands. They parallel the transitions that muscle cells undergo during differentiation. Modulation of β1 integrin adhesive function by alternative splicing serves as a physiological mechanism reinforcing the cytoskeleton– matrix link in muscle cells. This reflects the major role for β1D integrin in muscle, where extremely stable association is required for contraction.