Ostrowska Zofia, Moraczewska Joanna
Zakład Biochemii i Biologii Komórki, Wydział Nauk Przyrodniczych, Uniwersytet Kazimierza Wielkiego w Bydgoszczy.
Postepy Hig Med Dosw (Online). 2017 May 5;71(0):339-351. doi: 10.5604/01.3001.0010.3818.
Cofilins are evolutionary conserved proteins present in all Eukaryotic cells. Their primary function is dynamic reorganization of actin cytoskeleton. Two cofilin isoforms are known: cofilin 1, present in all studied non-muscle cells and in embryonic muscle cells, and cofilin 2, which dominates in mature skeletal and cardiac muscles. Polypeptide chains of both isoforms fold into a structure homological to a conservative ADF (actin depolymerizing factor) domain, which is characteristic of actin depolymerizing factor. In cofilin molecule two actin-binding sites were found. One site binds monomeric and filamentous actin, the second one interacts only with the filament. Binding of cofilin to actin filament causes a change in the orientation of subunits, which results in filament severing. This increases number of ends which can either elongate or shorten the filament, depending on the conditions. Cofilin interactions with monomeric actin decreases availability of polymerization-competent actin subunits. Cofilin activity is controlled by phosphorylation, binding membrane phospholipids, local pH and oxidative stress. Under conditions of oxidative stress oxidation of cysteine residues leads to formation of dimers, which are able to cross-link actin filaments. Stable actin-cofilin rods save cellular ATP, which is not used during active polymerization process. This facilitates faster cell recovery from the stress. The final cellular reaction on the environmental stimuli is a resultant of cofilin activity and activities of other actin-binding proteins, which function either synergistically or antagonistically. Due to the central role in the regulation of actin filaments dynamics, cofilin is involved in development of cancer, neurodegenerative diseases, congenital myopathies and cardiomyopathies.
丝切蛋白是存在于所有真核细胞中的进化保守蛋白。它们的主要功能是对肌动蛋白细胞骨架进行动态重组。已知有两种丝切蛋白亚型：丝切蛋白1，存在于所有已研究的非肌肉细胞和胚胎肌肉细胞中；丝切蛋白2，在成熟的骨骼肌和心肌中占主导地位。两种亚型的多肽链都折叠成与保守的肌动蛋白解聚因子（ADF）结构域同源的结构，这是肌动蛋白解聚因子的特征。在丝切蛋白分子中发现了两个肌动蛋白结合位点。一个位点结合单体肌动蛋白和丝状肌动蛋白，另一个位点仅与细丝相互作用。丝切蛋白与肌动蛋白丝的结合会导致亚基方向的改变，从而导致细丝切断。这增加了细丝末端的数量，根据条件不同，这些末端可以使细丝延长或缩短。丝切蛋白与单体肌动蛋白的相互作用会降低具有聚合能力的肌动蛋白亚基的可用性。丝切蛋白的活性受磷酸化、结合膜磷脂、局部pH值和氧化应激的控制。在氧化应激条件下，半胱氨酸残基的氧化会导致二聚体的形成，这些二聚体能够交联肌动蛋白丝。稳定的肌动蛋白-丝切蛋白棒节省了细胞ATP，而在活跃的聚合过程中不会消耗ATP。这有助于细胞更快地从应激中恢复。细胞对环境刺激的最终反应是丝切蛋白活性与其他肌动蛋白结合蛋白活性的结果，这些蛋白的功能要么协同要么拮抗。由于在调节肌动蛋白丝动力学中起核心作用，丝切蛋白参与了癌症、神经退行性疾病、先天性肌病和心肌病的发展。
