α-actinin revisited:: A fresh look at an old player
α-actinin revisited:: A fresh look at an old player
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DOI：
10.1002/cm.20007
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发表时间：
2004-06-01
影响因子：
--
通讯作者：
Carpen, O
中科院分区：
文献类型：
--
作者：
Otey, CA;Carpen, O
在过去的20年里，细胞生物学家的思想发生了根本性的变化，他们意识到细胞比以前认为的要优雅和高效得多。我们现在意识到，细胞生理学中存在大量冗余：如果一种生物功能确实是细胞生存的关键，那么通常有不止一种分子能够发挥这种功能。类似地，许多细胞蛋白质已经进化出高度的多功能性，并且能够在不同的细胞环境中服务于不同的目的。对于最近才发现的蛋白质，多功能性的想法很容易被接受，但许多经典的细胞骨架蛋白质是在更早的时候被发现的，当时简单化的“一种蛋白质，一种功能”观点占主导地位。α-辅肌动蛋白就是这样一种蛋白质;或者更确切地说，α-辅肌动蛋白是一个由四种密切相关的基因产物组成的家族，最初被描述为肌动蛋白交联蛋白。在过去的几年中，大量的文献表明，除了肌动蛋白外，α-辅肌动蛋白还具有大量的分子伴侣（见表1）。此外，α-辅肌动蛋白存在于多个亚细胞区域，包括细胞-细胞和细胞-基质接触部位、细胞突起、板状伪足和应力纤维致密区。因此，现在清楚的是，α-辅肌动蛋白在细胞中起着多种重要作用：它将细胞骨架连接到各种连接点中的许多不同的跨膜蛋白，它调节各种受体的活性，并且它作为支架将细胞骨架连接到不同的信号通路。本文将讨论最近的进展，突出了这种分子的作用和调节其活动的途径，特别关注α-辅肌动蛋白在非肌肉细胞中的功能。
Cell biologists have undergone a fundamental revision in their thinking in the past 20 years, with the realization that cells are far more elegant and efficient than was previously believed. We now appreciate that there is a great deal of redundancy built into cellular physiology: if a biological function is truly key to the survival of the cell, then there is usually more than one molecule able to serve that function. Similarly, many cellular proteins have evolved a high degree of versatility and are able to serve different purposes in different cellular contexts. For proteins that have been discovered only recently, the idea of multifunctionality is easy to swallow, but many classic cytoskeletal proteins were identified in an earlier time, when the simplistic “one protein, one function” view held sway. α-Actinin is one such protein; or rather, α-actinin is a family of four closely related gene products that were originally described as actin-crosslinking proteins. In the past few years, an accumulating body of literature has revealed that α-actinin possesses an exceptionally large number of molecular partners, in addition to actin (see Table I). Furthermore, α-actinin is present in multiple subcellular regions, including cell-cell and cell-matrix contact sites, cellular protrusions, lamellipodia and stress fiber dense regions. Thus, it is now clear that α-actinin plays multiple important roles in the cell: it links the cytoskeleton to many different transmembrane proteins in a variety of junctions, it regulates the activity of a variety of receptors, and it serves as a scaffold to connect the cytoskeleton to diverse signaling pathways. This review will discuss recent advances that highlight the expanding role of this molecule and the pathways that regulate its activities, with a particular focus on α-actinin’s functions in non-muscle cells.