The LINC Complex Transmits Integrin-dependent Tension to the Nuclear Lamina and Represses Epidermal Differentiation

Overview

Journal Elife

Specialty Biology

Date 2021 Mar 29

PMID 33779546

Citations 34

Authors

Emma Carley

Rachel M Stewart

Abigail Zieman

Iman Jalilian

Diane E King

Amanda Zubek

Samantha Lin

Valerie Horsley

Megan C King

Affiliations

Soon will be listed here.

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.

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