TY - JOUR
T1 - Nuclear lamin A/C harnesses the perinuclear apical actin cables to protect nuclear morphology
AU - Kim, Jeong Ki
AU - Louhghalam, Arghavan
AU - Lee, Geonhui
AU - Schafer, Benjamin W.
AU - Wirtz, Denis
AU - Kim, Dong Hwee
N1 - Funding Information:
We thank members of the Applied Mechanobiology Group at Korea University for fruitful discussions and Professor Kwan-Young Lee in the department of Chemical and Biomolecular Engineering at Korea University for generously providing guidance on project management. This work was supported by the KU-KIST Graduate School of Converging Science and Technology Program (R1435293), the National Research Foundation of Korea (R1610512), the Korea University Future Research Grant (K1719781), and National Cancer Institute (U54CA143868 and R01CA174388).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/12/1
Y1 - 2017/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85038827849&partnerID=8YFLogxK
U2 - 10.1038/s41467-017-02217-5
DO - 10.1038/s41467-017-02217-5
M3 - Article
C2 - 29242553
AN - SCOPUS:85038827849
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2123
ER -