Cyclase-associated protein 1 (CAP1) promotes cofilin-induced actin dynamics in mammalian nonmuscle cells
Cyclase-associated protein 1 (CAP1) promotes cofilin-induced actin dynamics in mammalian nonmuscle cells
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DOI：
10.1091/mbc.e04-01-0048
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发表时间：
2004-05-01
影响因子：
3.3
通讯作者：
Lappalainen, P
中科院分区：
文献类型：
--
作者：
Bertling, E;Hotulainen, P;Lappalainen, P
环酶相关蛋白(CAPS)是一种高度保守的肌动蛋白单体结合蛋白，存在于所有真核生物中。然而，CAP对肌动蛋白动力学的作用机制一直难以捉摸。在哺乳动物中，两种CAP亚型的存在使情况变得更加复杂，它们的差异尚未得到表征。在这里，我们发现CAP1在小鼠非肌肉细胞中广泛表达，而CAP2是发育中的横纹肌的主要亚型。在培养的NIH3T3和1316171细胞中，Cap1是一种高度丰富的蛋白质，它与cofilin-1共同定位于皮质肌动蛋白细胞骨架的动态区域。对Cap1基因敲除细胞的分析表明，该蛋白促进了肌动蛋白细丝的快速解聚，对细胞形态、迁移和内吞作用非常重要。有趣的是，Cap1的缺失导致Cofilin-1积聚到异常的细胞质聚集体中，并导致与Cofilin-1基因敲除细胞相似的细胞骨架缺陷，表明Cap1是ADF/Cofilin正确的亚细胞定位和功能所必需的。总之，这些数据提供了第一个直接的活体证据，证明CAP与ADF/cofilin一起促进了肌动蛋白的快速动力学，并且是哺乳动物几个中央细胞过程所必需的。
Cyclase-associated proteins (CAPs) are highly conserved actin monomer binding proteins present in all eukaryotes. However, the mechanism by which CAPs contribute to actin dynamics has been elusive. In mammals, the situation is further complicated by the presence of two CAP isoforms whose differences have not been characterized. Here, we show that CAP1 is widely expressed in mouse nonmuscle cells, whereas CAP2 is the predominant isoform in developing striated muscles. In cultured NIH3T3 and 1316171 cells, CAP1 is a highly abundant protein that colocalizes with cofilin-1 to dynamic regions of the cortical actin cytoskeleton. Analysis of CAP1 knockdown cells demonstrated that this protein promotes rapid actin filament depolymerization and is important for cell morphology, migration, and endocytosis. Interestingly, depletion of CAP1 leads to an accumulation of cofilin-1 into abnormal cytoplasmic aggregates and to similar cytoskeletal defects to those seen in cofilin-1 knockdown cells, demonstrating that CAP1 is required for proper subcellular localization and function of ADF/cofilin. Together, these data provide the first direct in vivo evidence that CAP promotes rapid actin dynamics in conjunction with ADF/cofilin and is required for several central cellular processes in mammals.