Chakravarty Devasmita, Vedula Pavan, Coffin Megan, Chen Li, Sterling Stephanie, Peshkova Alina D, Suzuki Aae, Zhao Liang, Patra Katrick, Assenmacher Charles-Antoine, Radaelli Enrico, Levine Mark, Litvinov Rustem I, Abrams Charles S, Fowler Velia M, Kashina Anna
Department of Biomedical Sciences, University of Pennsylvania, Philadelphia, PA 19104.
Department of Biological Sciences, University of Delaware, Newark, DE 19716.
Mol Biol Cell. 2025 Feb 1;36(2):ar18. doi: 10.1091/mbc.E24-04-0186. Epub 2024 Dec 20.
Actin is an essential component of the cytoskeleton in every eukaryotic cell. β-and γ-nonmuscle actin are over 99% identical to each other at the protein level but are encoded by different genes and play distinct roles in vivo. Blood cells, especially red blood cells (RBC), contain almost exclusively β-actin, and it has been generally assumed that this bias is dictated by the unique suitability of β-actin for RBC cytoskeleton function due to its specific amino acid sequence. Here we tested this assumption by analyzing the "β-coded γ-actin" (Actbcg) mouse model, in which the β-actin gene is edited by five-point mutations to produce γ-actin protein. Strikingly, despite lacking β-actin protein, Actbcg mice had no detectable phenotypes in RBCs, and no changes in the RBC shape, integrity, deformability, and molecular composition of their spectrin-based membrane skeleton. No actin-dependent changes were observed in platelets, another anucleate cell type enriched for β-actin. Our data show that, contrary to expectations, β-actin function in mature RBCs and platelets is independent of its protein sequence and therefore its enrichment in hematopoiesis and mature blood cells is likely driven entirely by its nucleotide-dependent functions.
肌动蛋白是每个真核细胞细胞骨架的重要组成部分。β-和γ-非肌肉肌动蛋白在蛋白质水平上彼此的相似度超过99%，但由不同基因编码，在体内发挥不同作用。血细胞，尤其是红细胞（RBC），几乎只含有β-肌动蛋白，人们普遍认为这种偏向是由β-肌动蛋白因其特定氨基酸序列而对红细胞细胞骨架功能具有独特适用性所决定的。在这里，我们通过分析“β编码γ-肌动蛋白”（Actbcg）小鼠模型来检验这一假设，在该模型中，β-肌动蛋白基因通过五点突变进行编辑以产生γ-肌动蛋白蛋白。令人惊讶的是，尽管缺乏β-肌动蛋白蛋白，但Actbcg小鼠的红细胞没有可检测到的表型，其基于血影蛋白的膜骨架的红细胞形状、完整性、变形性和分子组成也没有变化。在血小板中也未观察到肌动蛋白依赖性变化，血小板是另一种富含β-肌动蛋白的无核细胞类型。我们的数据表明，与预期相反，成熟红细胞和血小板中的β-肌动蛋白功能与其蛋白质序列无关，因此其在造血和成熟血细胞中的富集可能完全由其核苷酸依赖性功能驱动。
