Department of Cell Biology, New York University Grossman School of Medicine, New York, NY 10016, USA.
Dis Model Mech. 2024 Sep 1;17(9). doi: 10.1242/dmm.050729. Epub 2024 Aug 29.
The translation elongation factor eEF1α (eukaryotic elongation factor 1α) mediates mRNA translation by delivering aminoacyl-tRNAs to ribosomes. eEF1α also has other reported roles, including the regulation of actin dynamics. However, these distinct roles of eEF1α are often challenging to uncouple and remain poorly understood in aging metazoan tissues. The genomes of mammals and Drosophila encode two eEF1α paralogs, with eEF1α1 expressed ubiquitously and eEF1α2 expression more limited to neurons and muscle cells. Here, we report that eEF1α2 plays a unique role in maintaining myofibril homeostasis during aging in Drosophila. Specifically, we generated an eEF1α2 null allele, which was viable and showed two distinct muscle phenotypes. In young flies, the mutants had thinner myofibrils in indirect flight muscles that could be rescued by expressing eEF1α1. With aging, the muscles of the mutant flies began showing abnormal distribution of actin and myosin in muscles, but without a change in actin and myosin protein levels. This age-related phenotype could not be rescued by eEF1α1 overexpression. These findings support an unconventional role of Drosophila eEF1α2 in age-related homeostasis of muscle myofibers.
翻译延伸因子 eEF1α（真核延伸因子 1α）通过将氨酰基-tRNA 递送至核糖体来介导 mRNA 翻译。eEF1α 还有其他报道的作用，包括调节肌动蛋白动力学。然而，这些不同的 eEF1α 作用通常难以分离，在衰老的后生动物组织中仍然知之甚少。哺乳动物和果蝇的基因组编码两种 eEF1α 同源物，eEF1α1 广泛表达，而 eEF1α2 的表达更局限于神经元和肌肉细胞。在这里，我们报告 eEF1α2 在果蝇衰老过程中对维持肌原纤维内稳态起着独特的作用。具体来说，我们生成了一个 eEF1α2 缺失突变体，该突变体是有活力的，并且在间接飞行肌肉中表现出两种不同的肌肉表型。在年轻的果蝇中，突变体的肌原纤维在间接飞行肌肉中较细，用 eEF1α1 表达可以挽救。随着衰老，突变体肌肉中肌动蛋白和肌球蛋白的分布开始出现异常，但肌动蛋白和肌球蛋白蛋白水平没有变化。这种与年龄相关的表型不能通过 eEF1α1 的过表达来挽救。这些发现支持果蝇 eEF1α2 在与年龄相关的肌肉肌原纤维内稳态中的非传统作用。
