Supervillin modulation of focal adhesions involving TRIP6/ZRP-1.
Supervillin modulation of focal adhesions involving TRIP6/ZRP-1.
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DOI：
10.1083/jcb.200512051
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发表时间：
2006-07-31
影响因子：
7.8
通讯作者：
Luna, Elizabeth J
中科院分区：
文献类型：
--
作者：
Takizawa, Norio;Smith, Tara C;Nebl, Thomas;Crowley, Jessica L;Palmieri, Stephen J;Lifshitz, Lawrence M;Ehrhardt, Anka G;Hoffman, Laura M;Beckerle, Mary C;Luna, Elizabeth J
细胞-基质接触，称为粘着斑（FA），在快速移动的细胞中是动态的。我们表明，超绒毛蛋白（SV）--一种与此类细胞中的肌球蛋白II和F-肌动蛋白结合的外周膜蛋白--负调节应力纤维、FA和细胞与基质的粘附。SV（SV 342 -571）中的主要FA调节序列与zyxin家族中的两种蛋白质（甲状腺受体相互作用蛋白6（TRIP 6）和脂肪瘤首选伴侣（LPP））的LIM结构域结合，但不与zyxin本身结合。SV和TRIP 6在大型FA中共存，TRIP 6可能有助于招募SV。RNAi介导的任一蛋白质的减少增加细胞与纤连蛋白的粘附。TRIP 6部分挽救SV对应力纤维和FA的影响，显然是通过将SV与FA错位。因此，SV与TRIP 6在FA处的相互作用促进FA结构和功能的丧失。SV和TRIP 6结合伴侣提出了几种特定的机制，通过这些机制SV-TRIP 6相互作用可以调节FA成熟和/或分解。
Cell–substrate contacts, called focal adhesions (FAs), are dynamic in rapidly moving cells. We show that supervillin (SV)—a peripheral membrane protein that binds myosin II and F-actin in such cells—negatively regulates stress fibers, FAs, and cell–substrate adhesion. The major FA regulatory sequence within SV (SV342-571) binds to the LIM domains of two proteins in the zyxin family, thyroid receptor–interacting protein 6 (TRIP6) and lipoma-preferred partner (LPP), but not to zyxin itself. SV and TRIP6 colocalize within large FAs, where TRIP6 may help recruit SV. RNAi-mediated decreases in either protein increase cell adhesion to fibronectin. TRIP6 partially rescues SV effects on stress fibers and FAs, apparently by mislocating SV away from FAs. Thus, SV interactions with TRIP6 at FAs promote loss of FA structure and function. SV and TRIP6 binding partners suggest several specific mechanisms through which the SV–TRIP6 interaction may regulate FA maturation and/or disassembly.