The nuclear envelope protein Net39 is essential for muscle nuclear integrity and chromatin organization
Year: 2021
Type: article
Abstract: 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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,560
Funders: Welch Foundation, Moody Foundation, University of Texas Southwestern Medical Center, National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Arthritis and Musculoskeletal and Skin Diseases, Eunice Kennedy Shriver National Institute of Child Health and Human Development
Awards: Myoediting of Duchenne Muscular Dystrophy, G3770160408, Role of Twist2+ myogenic progenitor cells in adult skeletal muscle, TEM for UT Southwestern Electron Microscopy Core Facility, G5968285356, G6054505128, G662211534, Molecular Dissection of Myoblast Fusion In Muscle Development and Regeneration, Deciphering the role of a novel micropeptide in cardiac function and dysfunction, G9000111337, G9000159223, G9000181096, G9000291716
OpenAlex ID: W3125879591