Zasp regulates integrin activation
Zasp regulates integrin activation
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DOI：
10.1242/jcs.103291
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发表时间：
2012-12-01
影响因子：
4
通讯作者：
Calderwood, David A.
中科院分区：
文献类型：
--
作者：
Bouaouina, Mohamed;Jani, Klodiana;Calderwood, David A.
整合素是连接细胞外基质（ECM）和细胞骨架的异二聚体粘附受体。支架蛋白talin与β-整联蛋白的胞质尾区的结合引起整联蛋白异二聚体的胞外结构域的构象变化，从而允许ECM配体的高亲和力结合。这个重要的过程被称为整合素激活。在这里，我们报告的Z带选择性剪接PDZ基序包含蛋白（Zasp）与塔林合作，激活α 5 β 1整合素在哺乳动物组织培养和α PS2 β PS整合素在果蝇。Zasp是一种在人类心肌病中突变的含有PDZ-LIM结构域的蛋白质，以前被认为主要在肌肉收缩机制的组装和维持中起作用。值得注意的是，Zasp是第一个显示出与talin共激活α 5 β 1整联蛋白的蛋白质，并且似乎以与已知的α IIb β 3整联蛋白共激活剂不同的方式这样做。
Integrins are heterodimeric adhesion receptors that link the extracellular matrix (ECM) to the cytoskeleton. Binding of the scaffold protein, talin, to the cytoplasmic tail of beta-integrin causes a conformational change of the extracellular domains of the integrin heterodimer, thus allowing high-affinity binding of ECM ligands. This essential process is called integrin activation. Here we report that the Z-band alternatively spliced PDZ-motif-containing protein (Zasp) cooperates with talin to activate alpha 5 beta 1 integrins in mammalian tissue culture and alpha PS2 beta PS integrins in Drosophila. Zasp is a PDZ-LIM-domain-containing protein mutated in human cardiomyopathies previously thought to function primarily in assembly and maintenance of the muscle contractile machinery. Notably, Zasp is the first protein shown to co-activate alpha 5 beta 1 integrins with talin and appears to do so in a manner distinct from known alpha IIb beta 3 integrin co-activators.