Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Hamon Center for Regenerative Science and Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Nat Commun. 2021 Jan 29;12(1):690. doi: 10.1038/s41467-021-20987-x.
Lamins and transmembrane proteins within the nuclear envelope regulate nuclear structure and chromatin organization. Nuclear envelope transmembrane protein 39 (Net39) is a muscle nuclear envelope protein whose functions in vivo have not been explored. We show that mice lacking Net39 succumb to severe myopathy and juvenile lethality, with concomitant disruption in nuclear integrity, chromatin accessibility, gene expression, and metabolism. These abnormalities resemble those of Emery-Dreifuss muscular dystrophy (EDMD), caused by mutations in A-type lamins (LMNA) and other genes, like Emerin (EMD). We observe that Net39 is downregulated in EDMD patients, implicating Net39 in the pathogenesis of this disorder. Our findings highlight the role of Net39 at the nuclear envelope in maintaining muscle chromatin organization, gene expression and function, and its potential contribution to the molecular etiology of EDMD.
核膜中的核纤层和跨膜蛋白调节核结构和染色质组织。核膜跨膜蛋白 39（Net39）是一种肌肉核膜蛋白，其体内功能尚未被探索。我们发现缺乏 Net39 的小鼠会患上严重的肌病和幼年致死性疾病，同时伴随着核完整性、染色质可及性、基因表达和代谢的破坏。这些异常类似于由 A 型核纤层（LMNA）和其他基因（如 Emerin [EMD]）突变引起的 Emery-Dreifuss 肌营养不良症（EDMD）。我们观察到 Net39 在 EDMD 患者中下调，表明 Net39 参与了这种疾病的发病机制。我们的研究结果强调了 Net39 在维持肌肉染色质组织、基因表达和功能中的核膜作用，以及它对 EDMD 分子病因的潜在贡献。
