Overview of cellular homeostasis-associated nuclear envelope lamins and associated input signals

Abstract

With the discovery of the role of the nuclear envelope protein lamin in human genetic diseases, further diverse roles of lamins have been elucidated. The roles of lamins have been addressed in cellular homeostasis including gene regulation, cell cycle, cellular senescence, adipogenesis, bone remodeling as well as modulation of cancer biology. Features of laminopathies line with oxidative stress-associated cellular senescence, differentiation, and longevity and share with downstream of aging-oxidative stress. Thus, in this review, we highlighted various roles of lamin as key molecule of nuclear maintenance, specially lamin-A/C, and mutated LMNA gene clearly reveal aging-related genetic phenotypes, such as enhanced differentiation, adipogenesis, and osteoporosis. The modulatory roles of lamin-A/C in stem cell differentiation, skin, cardiac regulation, and oncology have also been elucidated. In addition to recent advances in laminopathies, we highlighted for the first kinase-dependent nuclear lamin biology and recently developed modulatory mechanisms or effector signals of lamin regulation. Advanced knowledge of the lamin-A/C proteins as diverse signaling modulators might be biological key to unlocking the complex signaling of aging-related human diseases and homeostasis in cellular process.

The NFATc1/P2X7 receptor relationship in human intervertebral disc cells

“…Particularly intriguing is the nuclear localization of P2X7R, which has been undeservedly underestimated until now. To explore this aspect further, we compared the localization of P2X7R and lamin A/C, an important component of the nuclear lamina playing many roles in healthy and diseased cells, including maintenance of structural stability, cell motility, mechanosensing, chromosome organization, gene regulation, cell differentiation, DNA damage repair, and telomere Frontiers in Cell and Developmental Biology frontiersin.org protection (Lattanzi et al, 2012;Kim et al, 2023). We found, for the first time, that P2X7R is not only localized in the nuclear matrix but also at the nuclear lamina and co-localized with lamin A/C, as revealed by the immunofluorescence experiments shown in Figure 3D.…”