Nuclear lamin A/C harnesses the perinuclear apical actin cables to protect nuclear morphology

• Published in: Nature communications 2017-12, Vol.8 (1), p.2123-13, Article 2123
• Main Authors: Kim, Jeong-Ki, Louhghalam, Arghavan, Lee, Geonhui, Schafer, Benjamin W., Wirtz, Denis, Kim, Dong-Hwee
• Format: Article
• Language: English
• Subjects: 631/80/128/2031; 631/80/386/1700; 631/80/386/1899; Actin; Actin Cytoskeleton - metabolism; Actins - metabolism; Animals; Auditory defects; Cables; Cell Nucleus - metabolism; Cells, Cultured; Cytoskeleton; Deformation; Deformation mechanisms; Deformation resistance; Embryo fibroblasts; Embryo, Mammalian - cytology; Embryo, Mammalian - metabolism; Embryos; Fibroblasts; Fibroblasts - cytology; Fibroblasts - metabolism; Harnesses; Homeostasis; Humanities and Social Sciences; Intracellular signalling; Lamin Type A - genetics; Lamin Type A - metabolism; Mathematical morphology; Mechanical stimuli; Mechanotransduction; Mechanotransduction, Cellular; Mice, Knockout; Microscopy, Confocal; Morphology; multidisciplinary; Nuclear deformation; Nuclei; Nuclei (cytology); Science; Science (multidisciplinary); Stress, Mechanical; Structural integrity
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-017-02217-5

The distinct spatial architecture of the apical actin cables (or actin cap) facilitates rapid biophysical signaling between extracellular mechanical stimuli and intracellular responses, including nuclear shaping, cytoskeletal remodeling, and the mechanotransduction of external forces into biochemical signals. These functions are abrogated in lamin A/C-deficient mouse embryonic fibroblasts that recapitulate the defective nuclear organization of laminopathies, featuring disruption of the actin cap. However, how nuclear lamin A/C mediates the ability of the actin cap to regulate nuclear morphology remains unclear. Here, we show that lamin A/C expressing cells can form an actin cap to resist nuclear deformation in response to physiological mechanical stresses. This study reveals how the nuclear lamin A/C-mediated formation of the perinuclear apical actin cables protects the nuclear structural integrity from extracellular physical disturbances. Our findings highlight the role of the physical interactions between the cytoskeletal network and the nucleus in cellular mechanical homeostasis. An actin cap protects the morphology of the nucleus during cellular mechanical stress. Here, the authors show that the nuclear lamina protein lamin A/C mediates the formation of the actin cap in response to stress, and model the distribution of forces in the presence and absence of the actin cap.