The Form and Function of PIEZO2

Abstract

Mechanosensation is the ability to detect dynamic mechanical stimuli (e.g., pressure, stretch, and shear stress) and is essential for a wide variety of processes, including our sense of touch on the skin. How touch is detected and transduced at the molecular level has proved to be one of the great mysteries of sensory biology. A major breakthrough occurred in 2010 with the discovery of a family of mechanically gated ion channels that were coined PIEZOs. The last 10 years of investigation have provided a wealth of information about the functional roles and mechanisms of these molecules. Here we focus on PIEZO2, one of the two PIEZO proteins found in humans and other mammals. We review how work at the molecular, cellular, and systems levels over the past decade has transformed our understanding of touch and led to unexpected insights into other types of mechanosensation beyond the skin.

Transcription Factor Acj6 Controls Dendrite Targeting via Combinatorial Cell-Surface Codes

“…We identified many Acj6 executors via both loss-of-function and rescue experiments. These include the fly ortholog of the mechanosensitive ion channel Piezos 38,39 , which mediate somatosensory and interoceptive mechanotransduction and cell volume regulation 23,40-45 . Piezo also regulates neurodevelopmental processes and axon regeneration 46-48 .…”

“…Since the discovery of Piezo1 and Piezo2 (Coste et al, 2010), numerous functions of the Piezo protein family have been uncovered in a wide range of physiological contexts, including but not limited to somatosensory and interoceptive mechanotransduction and cell volume regulation (reviewed in Murthy et al, 2017; Szczot et al, 2021). Piezo has also been shown to regulate neurodevelopmental processes and axon regeneration—it promotes neurogenesis instead of astrogenesis in human neural stem cells (Pathak et al, 2014), contributes to axon growth and targeting of Xenopus retinal ganglion cells (Koser et al, 2016), and cell autonomously inhibits axon regeneration (Song et al, 2019).…”

Force From Filaments: The Role of the Cytoskeleton and Extracellular Matrix in the Gating of Mechanosensitive Channels

“…Membrane stretch, indentation, and substrate deformation described above have been classically applied in a low-throughput setting. A review summarized the corresponding methods for high-throughput stimulation that may be feasible for mechanical screening of MS ion channels ( Szczot et al, 2021 ).…”

“…Subsequent studies have revealed new roles of PIEZOs in touch, mechanical pain, itch, proprioception, breathing, gastrointestinal tract, bladder, baroreflex, hearing, cartilage, bone development, etc. ( Murthy et al, 2017 ; Szczot et al, 2021 ). Mutations in PIEZO1 and PIEZO2 are linked to multiple hereditary human diseases ( Volkers et al, 2015 ; Alper, 2017 ).…”

“…In the fourth criterion, because of the requirement of auxiliary subunits such as specific ECM- and cytoskeleton-associated proteins, the pore-forming subunits gated by force-from-filament to fit the criterion is challenging. From ENaC/DEG-superfamily to PIEZO1/2, a series of reviews have summarized the detailed information about the identified or confirmed MS ion channels, covering the biophysical properties of the structure to the biological function to show how the specific mechanotransduction regulates and balances the physiologic conditions ( Chalfie, 2009 ; Árnadóttir and Chalfie, 2010 ; Katta et al, 2015 ; Ranade et al, 2015 ; Martino et al, 2018 ; Jin et al, 2020 ; Nicoletti et al, 2021 ; Szczot et al, 2021 ). However, there is not much discussion on the auxiliary subunits involved in the force-from-filament.…”