Kervella Marie, Muchir Antoine
PhyMedExp, University of Montpellier, INSERM, CNRS, Montpellier, France.
Sorbonne Université, INSERM U974, Institute of Myology, Center of Research in Myology, Paris, France.
Subcell Biochem. 2025;115:1-22. doi: 10.1007/978-3-032-00537-3_1.
Nuclear lamins, the unique type 5 intermediate filaments of the nucleus, form a structural network beneath the nuclear envelope. Through their strategic localization, they interact with numerous partners and regulate a wide range of biochemical and biophysical processes. In load-bearing tissues such as the heart, nuclear lamins are crucial for maintaining mechanical integrity and genome stability during cardiac contraction. By associating with chromatin through lamina-associated domains, they play a fundamental role in genome organization and gene expression. Disruption of the nuclear lamin meshwork in CardioLaminopathy leads to chromatin remodeling and dysregulated gene expression. Although the precise cellular and molecular mechanisms driving CardioLaminopathy remain incompletely understood, alterations in genome organization are emerging as key contributors to disease pathogenesis and progression.
核纤层蛋白是细胞核中独特的第5型中间丝,在核膜下方形成一个结构网络。通过其战略性定位,它们与众多伙伴相互作用,并调节广泛的生化和生物物理过程。在心脏等承重组织中,核纤层蛋白对于在心脏收缩期间维持机械完整性和基因组稳定性至关重要。通过层粘连相关结构域与染色质结合,它们在基因组组织和基因表达中发挥着重要作用。心脏核纤层蛋白病中核纤层网络的破坏会导致染色质重塑和基因表达失调。尽管驱动心脏核纤层蛋白病的确切细胞和分子机制仍未完全了解,但基因组组织的改变正在成为疾病发病机制和进展的关键因素。