School of Biological Sciences, Indian Association for the Cultivation of Science, Kolkata, West Bengal, India.
Laboratory of Molecular Physiology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
J Biol Chem. 2023 Sep;299(9):105143. doi: 10.1016/j.jbc.2023.105143. Epub 2023 Aug 9.
Recent genomic studies reported that 90 to 95% of human genes can undergo alternative splicing, by which multiple isoforms of proteins are synthesized. However, the functional consequences of most of the isoforms are largely unknown. Here, we report a novel alternatively spliced isoform of nonmuscle myosin IIA (NM IIA), called NM IIA2, which is generated by the inclusion of 21 amino acids near the actin-binding region (loop 2) of the head domain of heavy chains. Expression of NM IIA2 is found exclusively in the brain tissue, where it reaches a maximum level at 24 h during the circadian rhythm. The actin-dependent Mg-ATPase activity and in vitro motility assays reveal that NM IIA2 lacks its motor activities but localizes with actin filaments in cells. Interestingly, NM IIA2 can also make heterofilaments with NM IIA0 (noninserted isoform of NM IIA) and can retard the in vitro motility of NM IIA, when the two are mixed. Altogether, our findings provide the functional importance of a previously unknown alternatively spliced isoform, NM IIA2, and its potential physiological role in regulating NM IIA activity in the brain.
最近的基因组研究报告称，90%到 95%的人类基因可以进行选择性剪接，从而合成多种蛋白质异构体。然而，大多数异构体的功能后果在很大程度上仍是未知的。在这里，我们报道了一种非肌肉肌球蛋白 IIA（NM IIA）的新型选择性剪接异构体，称为 NM IIA2，它是通过在重链头部结构域的肌动蛋白结合区（环 2）附近插入 21 个氨基酸而产生的。NM IIA2 的表达仅在脑组织中发现，在昼夜节律中，其在 24 小时达到最大值。肌动蛋白依赖性 Mg-ATP 酶活性和体外运动性测定表明，NM IIA2 缺乏其运动活性，但在细胞中与肌动蛋白丝定位。有趣的是，NM IIA2 还可以与 NM IIA0（NM IIA 的非插入异构体）形成异源丝，并在两者混合时减缓 NM IIA 的体外运动性。总之，我们的发现提供了一个以前未知的选择性剪接异构体 NM IIA2 的功能重要性及其在调节大脑中 NM IIA 活性方面的潜在生理作用。
