The LINC complex transmits integrin-dependent tension to the nuclear lamina and represses epidermal differentiation
Year: 2021
Type: article
Abstract: While the mechanisms by which chemical signals control cell fate have been well studied, the impact of mechanical inputs on cell fate decisions is not well understood. Here, using the well-defined system of keratinocyte differentiation in the skin, we examine whether and how direct force transmission to the nucleus regulates epidermal cell fate. Using a molecular biosensor, we find that tension on the nucleus through linker of nucleoskeleton and cytoskeleton (LINC) complexes requires integrin engagement in undifferentiated epidermal stem cells and is released during differentiation concomitant with decreased tension on A-type lamins. LINC complex ablation in mice reveals that LINC complexes are required to repress epidermal differentiation in vivo and in vitro and influence accessibility of epidermal differentiation genes, suggesting that force transduction from engaged integrins to the nucleus plays a role in maintaining keratinocyte progenitors. This work reveals a direct mechanotransduction pathway capable of relaying adhesion-specific signals to regulate cell fate.
Source: eLife
DOI: 10.7554/elife.58541
Institution: Yale University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,500
Awards: Extrinsic Regulation of Epidermal Homeostatasis, Mechanisms that Regulate Skin Wound Healing, Predoctoral Program in Cellular and Molecular Biology, Examining the Role of the LINC Complex in Modulating Adhesion and Cytoskeletal Tension in the Myocardium, Remodeling of the structure and function of the nuclear lamina by LINC complex-dependent tension, Training in Investigative Dermatology
OpenAlex ID: W3150522305