Emerging roles and mechanisms of ERK pathway mechanosensing

Abstract

The coupling between mechanical forces and modulation of cell signalling pathways is essential for tissue plasticity and their adaptation to changing environments. Whilst the number of physiological and pathological relevant roles of mechanotransduction has been rapidly expanding over the last decade, studies have been mostly focussing on a limited number of mechanosensitive pathways, which include for instance Hippo/YAP/TAZ pathway, Wnt/β-catenin or the stretch-activated channel Piezo. However, the recent development and spreading of new live sensors has provided new insights into the contribution of ERK pathway in mechanosensing in various systems, which emerges now as a fast and modular mechanosensitive pathway. In this review, we will document key in vivo and in vitro examples that have established a clear link between cell deformation, mechanical stress and modulation of ERK signalling, comparing the relevant timescale and mechanical stress. We will then discuss different molecular mechanisms that have been proposed so far, focussing on the epistatic link between mechanics and ERK and discussing the relevant cellular parameters affecting ERK signalling. We will finish by discussing the physiological and the pathological consequences of the link between ERK and mechanics, outlining how this interplay is instrumental for self-organisation and long-range cell–cell coordination.

MEK inhibitors: a promising targeted therapy for cardiovascular disease

“…Several studies showed that ERK activation is an essential adaptive mechanism that promotes cardiomyocyte survival during early stress ( 57 – 60 ). Moreover, ERK signaling controls the cellular response to mechanical forces ( 61 ), critical for an organ that contracts cyclically throughout life.…”