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Review
. 2023 May 12:11:1173514.
doi: 10.3389/fcell.2023.1173514. eCollection 2023.

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

Hyeong Jae Kim  1 , Peter C W Lee  2 , Jeong Hee Hong  1
Affiliations
Review

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

Hyeong Jae Kim et al. Front Cell Dev Biol. .

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.

Keywords: cell cycle; lamin; nuclear envelope; redox hemostasis; scenescence.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Structural illustration of lamin-A/C. The lamin-A and its isoform C comprise alternative splice variants. NLS, nuclear location signal.
FIGURE 2
FIGURE 2
Structural illustration of lamin-A/C-interacting molecules with filamentous structure. NPC, nuclear pore complexes, LINC, linker of nucleoskeleton and cytoskeleton, LEM domain-containing proteins (Emerin, LAP2, and MAN1), BAF: barrier to autointegration factor, LBR: lamin B receptor, NET: nuclear envelope transmembrane proteins (Patil and Sengupta, 2021).
FIGURE 3
FIGURE 3
Various roles of lamin-A/C on multiple cellular systems. Various studies have addressed the multiple disordered spectra of lamin mutations and we summarized the diversity of lamin-A/C function.
FIGURE 4
FIGURE 4
Schematic illustration of aberrantly expressed lamin-A/C in MSCs. Downregulated lamin-A/C induces adipogenesis and aging feature such as osteopenia and sarcopenia. MSC, mesenchymal stem cell; PPARγ, peroxisome proliferator activator gamma.
FIGURE 5
FIGURE 5
Schematic illustration of aberrantly expressed lamin-A/C in bone system. Abnormal expression of lamin induces osteoporosis which caused by upregulated RANKL and bone resorption and downregulated osteoblastic function, RunX2, osteocalcin, and phosphatase activity. RANKL, Receptor activator of NF-κB ligand; Runx2, Runt-related transcription factor 2.
FIGURE 6
FIGURE 6
Schematic illustration of lamin-A/C in skin development. Abnormal overexpression of lamin-A/C induces hyperproliferative keratinocyte with upregulated signaling modulators. BMP2, bone morphogenetic protein 2.
FIGURE 7
FIGURE 7
Schematic illustration of lamin mutations in cardiac system. Cardiomyopathy symptoms are occurred by misregulation of MAPK and WNT/β-catenin in mutant mouse models of Lmna (Lmna-null, Lmna H222P/H222P, Lmna N195K/N195K, and Lmna M371K).
See this image and copyright information in PMC

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