The actin filament as a mechno-sensing machinery

“力”在细胞生物学中具有广泛的生物学作用，包括细胞生存、发育、伤口愈合和生长的信号通路。一般认为，力通过膜中的拉伸激活离子通道启动信号转导，但最近有人提出，力也可能通过细胞骨架-基质连接的改变启动信号转导。细胞可能使用离子通道以外的机制来感知力，如肌动蛋白丝。本研究直接证明了单个肌动蛋白丝作为机械传感器，并通过体外重组系统调节cofilin的酶活性；我们制备了一根用光学镊子拉伸的肌动蛋白丝，并在丝中存在或不存在机械张力的情况下对其施加cofilin。令人惊讶的是，它证明了单个肌动蛋白丝的机械张力阻止了它被cofilin切断，这为肌动蛋白丝作为张力传感器并以张力依赖的方式调节cofilin切断能力的模型提供了强有力的支持。这是第一次证明某种蛋白质的张力调节了对调节蛋白质的敏感性。我们研究了肌动蛋白丝这种特殊性质的分子机制，并证明了这种机制在活细胞中起作用的数据。

Wide range of biological roles have been proposed for "force" in cell biology, including cell signal pathways for survival, development, wound healing, and growth. It is generally believed that force initiates signal transduction via stretch activated ion channels in the membrane, but recently it is suggested that force may also initiate signal transduction via changes in cytoskeletal-matrix linkages. Cells may use mechanisms other than ion channels to sense forces such as an actin filament. This study directly demonstrate that a single actin filament works as a mechano-sensor and regulates the enzymatic activity of cofilin by employing an in vitro reconstituted system ; we have prepared a single actin filament stretched with optical tweezers and applied cofilin to it in the presence or absence of mechanical tension in the filament. Surprisingly, it demonstrated that mechanical tension in the single actin filament prevented it from the severing by cofilin, providing a strong support for the model in which the actin filament acts as a tension-sensor and regulates the severing ability of cofilin in a tension-dependent manner. This is the first demonstration that tension in a certain protein regulates the susceptibility to the modulating proteins. We examined the molecular mechanism underlying this peculiar property of actin filament, and also demonstrate data that this mechanism works in living cells.