Piezo channels contribute to the regulation of myelination in Schwann cells

Abstract

Peripheral nerves and Schwann cells have to sustain constant mechanical constraints, caused by developmental growth as well as stretches associated with movements of the limbs and mechanical compressions from daily activities. In Schwann cells, signaling molecules sensitive to stiffness or stretch of the extracellular matrix, such as YAP/TAZ, have been shown to be critical for Schwann cell development and peripheral nerve regeneration. YAP/TAZ have also been suggested to contribute to tumorigenesis, neuropathic pain, and inherited disorders. Yet, the role of mechanosensitive ion channels in myelinating Schwann cells is vastly unexplored. Here we comprehensively assessed the expression of mechanosensitive ion channels in Schwann cells and identified that PIEZO1 and PIEZO2 are among the most abundant mechanosensitive ion channels expressed by Schwann cells. Using classic genetic ablation studies, we show that PIEZO1 is a transient inhibitor of radial and longitudinal myelination in Schwann cells. Contrastingly, we show that PIEZO2 may be required for myelin formation, as the absence of PIEZO2 in Schwann cells delays myelin formation. We found an epistatic relationship between PIEZO1 and PIEZO2, at both the morphological and molecular levels. Finally, we show that PIEZO1 channels affect the regulation of YAP/TAZ activation in Schwann cells. Overall, we present here the first demonstration that PIEZO1 and PIEZO2 contribute to mechanosensation in Schwann cells as well myelin development in the peripheral nervous system.

Mechanosensitive channel Piezo1 is an essential regulator in cell cycle progression of optic nerve head astrocytes

“…Transcriptional regulator YAP senses and responds to mechanical change through nuclear translocation, and its nuclear activation promotes cell proliferation. Piezo1 has been reported to regulate YAP activation in Schwann cells, another type of glial cells in the nervous system (Acheta et al, 2022). Therefore, we focused on the YAP to explore the mechanism involving Piezo1‐loss‐induced cell cycle arrest.…”

“…For example, Piezo1 promotes concerted activation of NFATc1, YAP1, and β‐catenin transcription factors to facilitate osteoblast differentiation during bone development (Zhou et al, 2020). Moreover, Piezo1 regulated YAP/TAZ activation in Schwann cells and contributed to myelin development in the peripheral nervous system (Acheta et al, 2022). Based on our study, The mechanosensitive transcription factor YAP is closely associated with the function of Piezo1, and the Piezo1‐YAP signaling contributes to ONH astrocytes proliferation.…”

Mechanical properties of the brain: Focus on the essential role of Piezo1‐mediated mechanotransduction in the CNS

“…Piezo1 is an inhibitor of Piezo2 (Acheta et al, 2022). In addition, Piezo1 and Piezo2 are both robustly expressed in articular chondrocytes, synergistically promoting mechanically mediated Ca 2+ signaling in chondrocytes and promoting mechanical strain-mediated cell damage following injury (Lee et al, 2014).…”

“…Numerous studies have shown that Piezo1 is a negative regulator of myelin formation in oligodendrocytes and Schwann cells (Acheta et al, 2022;Li et al, 2021;. Piezo1 is highly active after axonal injury and during axonal regeneration (Segel et al, 2019;, which may exacerbate nerve dam- et al, 2022).…”

The emerging roles of piezo1 channels in animal models of multiple sclerosis

“…It showed that both Piezo1 and Piezo2 are highly expressed in Schwann cells, but they have different roles in myelination. Piezo1 inhibits radial and longitudinal myelination while Piezo2 is required for myelin formation in the peripheral nervous system (PNS) ( 72 ). But whether Piezo2 is involved in MS remains unstudied.…”