据研究人员介绍,蛋白质的合成一般从一个甲硫氨酸开始,并在翻译过程中被去除。然而,细胞质肌动蛋白违背了这一规则,因为它的合成涉及到翻译后由一种身份不明的酶对乙酰化甲硫氨酸的非经典切除。
研究人员确定C19orf54,即ACTMAP(肌动蛋白成熟蛋白酶),就是这种酶。它的敲减导致小鼠细胞骨架在所有组织中都是由不成熟的肌动蛋白分子组成。然而,在骨骼肌中,肌节肌动蛋白丝的长度变短,肌肉功能下降,集中的细胞核(肌病的一个常见标志)逐渐积累。因此,ACTMAP编码成熟肌动蛋白合成所需的缺失因子,并在体内调节特定的肌动蛋白依赖性特征。
附:英文原文
Title: Actin maturation requires the ACTMAP/C19orf54 protease
Author: Peter Haahr, Ricardo A. Galli, Lisa G. van den Hengel, Onno B. Bleijerveld, Justina Kazokait-Adomaitien, Ji-Ying Song, Lona J. Kroese, Paul Krimpenfort, Marijke P. Baltissen, Michiel Vermeulen, Coen A. C. Ottenheijm, Thijn R. Brummelkamp
Issue&Volume: 2022-09-30
Abstract: Protein synthesis generally starts with a methionine that is removed during translation. However, cytoplasmic actin defies this rule because its synthesis involves noncanonical excision of the acetylated methionine by an unidentified enzyme after translation. Here, we identified C19orf54, named ACTMAP (actin maturation protease), as this enzyme. Its ablation resulted in viable mice in which the cytoskeleton was composed of immature actin molecules across all tissues. However, in skeletal muscle, the lengths of sarcomeric actin filaments were shorter, muscle function was decreased, and centralized nuclei, a common hallmark of myopathies, progressively accumulated. Thus, ACTMAP encodes the missing factor required for the synthesis of mature actin and regulates specific actin-dependent traits in vivo.
DOI: abq5082
Source: https://www.science.org/doi/10.1126/science.abq5082