A critical role for Piezo2 channels in the mechanotransduction of mouse proprioceptive neurons

Florez-Paz, Danny M.; Bali, Kiran Kumar; Kuner, Rohini; Gomis, Ana

doi:10.1038/srep25923

Cited by 92 publications

(91 citation statements)

References 29 publications

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“…S-1A). The specificity of the Piezo2-Ab1 was also demonstrated in a recent study on Piezo2 expression in the mesencephalic trigeminal nucleus 30 . While this positively-tested Piezo2-antibody worked only with limited sensitivity in immunohistochemistry on DRG (Supporting Fig.…”

Section: Identification Of Proteins Associated With Native Piezo2 Inmentioning

confidence: 71%

Native Piezo2 Interactomics Identifies Pericentrin as a Novel Regulator of Piezo2 in Somatosensory Neurons

et al. 2016

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The ability of somatosensory neurons to perceive mechanical stimuli relies on specialized mechanotransducing proteins and their molecular environment. Only recently has the identity of a major transducer of mechanical forces in vertebrates been revealed by the discovery of Piezo2. Further work has established its pivotal role for innocuous touch in mice. Therefore, Piezo2 offers a unique platform for the molecular investigation of somatosensory mechanosensation. We performed a mass spectrometry-based interactomics screen on native Piezo2 in somatosensory neurons of mouse dorsal root ganglia (DRG). Stringent and quantitative data analysis yielded the identity of 36 novel binding partners of Piezo2. The biological significance of this data set is reflected by functional experiments demonstrating a role for Pericentrin in modulating Piezo2 activity and membrane expression in somatosensory neurons. Collectively, our findings provide a framework for understanding Piezo2 physiology and serve as a rich resource for the molecular dissection of mouse somatosensation.

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Section: Identification Of Proteins Associated With Native Piezo2 Inmentioning

confidence: 71%

Native Piezo2 Interactomics Identifies Pericentrin as a Novel Regulator of Piezo2 in Somatosensory Neurons

et al. 2016

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“…Likewise, an inducible knockout of Piezo2 from dorsal root ganglion (DRG) neurons ( Advil-creERT2;Piezo2 fl ) , nearly abolishes rapidly-adapting, mechanically activated currents in these cells, causing severe deficits in multiple assays designed to test response to innocuous touch and gait stability [33]. The latter phenotype pointed to a role in proprioception, which was more clearly probed by two mouse models: a proprioceptive-specific DRG knockout ( Pvalb- Cre;Piezo2 fl/f ), which lead to severely impaired limb coordination, and a knockout from proprioceptive neurons of the mesencephalic trigeminal nucleus, which lead to impairments in coordination and balance [36, 37]. Piezo2 also mediates mechanosensitive currents in enterochromaffin cells from mouse small bowel [38].…”

Section: Physiology Of Piezo Mechanotransductionmentioning

confidence: 99%

Touch, Tension, and Transduction – The Function and Regulation of Piezo Ion Channels

Lewis

Grandl

2017

Trends in Biochemical Sciences

427

381

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In 2010, two proteins, Piezo1 and Piezo2, were identified as the long-sought molecular carriers of an excitatory mechanically activated current found in many cells. This discovery has opened the floodgates for studying a vast number of mechanotransduction processes. Over the past six years, groundbreaking research has identified Piezos as ion channels that sense light touch, proprioception, and vascular blood flow, ruled out roles for Piezos in several other mechanotransduction processes, and revealed the basic structural and functional properties of the channel. Here, we review these findings and discuss the many aspects of Piezo function that remain mysterious, including how Piezos convert a variety of mechanical stimuli into channel activation and subsequent inactivation, and what molecules and mechanisms modulate Piezo function.

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“…In the case of Piezo2, most studies to date have focused on Piezo2 expression in the peripheral nervous system and its key mechanotransduction roles in gentle touch, proprioception, and the regulation of breathing and blood pressure (Coste et al, 2010;Ranade et al, 2014;Woo et al, 2014;2015;Usoskin et al, 2015;Florez-Paz et al, 2016;Nonomura et al, 2017;Zeng et al, 2018). However, Venkata Sajja and colleagues have demonstrated, using RT-PCR and Western blotting using a commercial anti-Piezo2 antibody (Ab), that Piezo2 is expressed in rat neocortical and hippocampal tissue, and this expression is increased in response to repetitive mechanical (i.e., blast) injury (Sajja et al, 2014, Heyburn et al, 2019.…”

Section: Introductionmentioning

confidence: 99%

Piezo2, a pressure sensitive channel is expressed in select neurons of the mouse brain: a putative mechanism for synchronizing neural networks by transducing intracranial pressure pulses

Wang

Hamill

2020

Preprint

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Piezo2 expression in the normal, young adult mouse brain was examined using an anti-PIEZO2 Ab generated against a C-terminal fragment of the human PIEZO2 protein. As a positive control for Ab staining of mouse neurons, the Ab was shown to stain the majority (~90%) of mouse dorsal root ganglia (DRG) neurons, consistent with recent in situ hybridization and transcriptomic studies that also indicate Piezo2 gene expression in ~90% mouse DRG neurons.As a negative control and stringent test for specificity, the Ab failed to stain DRG satellite glial cells, which do not express Piezo2 but rather its paralog, Piezo1. In slices of brains isolated from the same mice as the DRG, the Ab displayed high selectivity in staining only specific neuron types, including some pyramidal neurons in the neocortex and hippocampus, Purkinje cells in the cerebellar cortex, and most notably mitral cells within the olfactory bulb. Given the demonstrated role of Piezo2 channels in peripheral neurons as a low-threshold pressure sensor (i.e., ≤ 5 mm Hg) critical for gentle touch, proprioception, and the regulation of breathing and blood pressure, its expression in select brain neurons has interesting implications. In particular, we propose that the pressure sensitive channel may provide specific brain neurons with an intrinsic resonance that acts to synchronize their firing with the normal pulsatile changes in intracranial pressure (ICP) associated with breathing and cardiac cycles. This novel mechanism could serve to increase the robustness of the respiration entrained oscillations that have been recorded in both rodent and human brains across widely distributed neuronal networks. The idea of a "global rhythm" within the brain has been mainly related to the effect of nasal airflow activating mechanosensitive neurons within the olfactory epithelium, which in turn synchronize, through direct synaptic connections, mitral neurons within the olfactory bulb and then through their projections, the activity of neural networks in other brain regions, including the hippocampus and neocortex. Our proposed, non-synaptic, intrinsic resonance mechanism for tracking pulsatile ICP changes would have the advantage that spatially separated brain networks could be globally synchronized effectively at the speed of sound.

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A critical role for Piezo2 channels in the mechanotransduction of mouse proprioceptive neurons

Cited by 92 publications

References 29 publications

Native Piezo2 Interactomics Identifies Pericentrin as a Novel Regulator of Piezo2 in Somatosensory Neurons

Native Piezo2 Interactomics Identifies Pericentrin as a Novel Regulator of Piezo2 in Somatosensory Neurons

Touch, Tension, and Transduction – The Function and Regulation of Piezo Ion Channels

Piezo2, a pressure sensitive channel is expressed in select neurons of the mouse brain: a putative mechanism for synchronizing neural networks by transducing intracranial pressure pulses

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