Abstract
Cellular processes are initiated and regulated by different stimuli, including mechanical forces. Cell membrane mechanosensors represent the first step towards the conversion of mechanical stimuli to a biochemical or electrical response. Mechanosensitive (MS) ion channels form a growing family of ion gating channels that respond to direct physical force or plasma membrane deformations. A number of calcium (Ca2+) permeable MS channels are known to regulate the initiation, direction, and persistence of cell migration during development and tumour progression. While the evidence that links individual MS ion channels to cell migration is growing, a unified analysis of the molecular mechanisms regulated downstream of MS ion channel activation is lacking. In this review, we describe the MS ion channel families known to regulate cell migration. We discuss the molecular mechanisms that act downstream of MS ion channels with an emphasis on Ca2+ mediated processes. Finally, we propose the future directions and impact of MS ion channel activity in the field of cell migration.
Highlights
Living organisms are exposed to a wide array of mechanical cues, from universal forces like gravity to microscopically localized stimuli such as fluid shear stress in blood vessels (Lu and Kassab, 2011), compression by neighbouring tissues (Barriga et al, 2018; Kim et al, 2017), or extracellular matrix stiffness (Chaudhuri et al, 2020)
This review aims to provide the reader with a unified understanding of the molecular mechanisms by which MS ion channels regulate cell migration
While both Piezo1 and TRPV4 have been linked to roles in regulating actin structures and modifying cell shape, their function appears to have high specificity and the overall effect on cell migration can drastically change depending on the specific actin fibres interacting with the MS ion channel
Summary
Living organisms are exposed to a wide array of mechanical cues, from universal forces like gravity to microscopically localized stimuli such as fluid shear stress in blood vessels (Lu and Kassab, 2011), compression by neighbouring tissues (Barriga et al, 2018; Kim et al, 2017), or extracellular matrix stiffness (Chaudhuri et al, 2020). An important family of mechanosensors are mechanosensitive (MS) ion channels, which are pore-forming protein structures localized in the cell plasma membrane and the membrane of certain organelles, i.e. the endoplasmic reticulum, endosomes, and lysosomes (Dong et al, 2010; Dong et al, 2008; Santana et al, 2019). MS ion channels are an important link between mechanical stimuli and Ca2+ mediated signalling and have been described to regulate the initiation, persis tence, and directionality of cell migration. This review aims to provide the reader with a unified understanding of the molecular mechanisms by which MS ion channels regulate cell migration. We present a detailed analysis of the pathways and mechanisms of action downstream of MS ion channels during mecha notransduction in cell migration, with emphasis on Ca2+ mediated sig nalling. We outline the emerging MS ion channels and discuss the key future directions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
