The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration

Song, Yuanquan; Li, Dan; Farrelly, Olivia; Miles, Leann; Li, Feng; Kim, Sung Eun; Lo, Tsz Y.; Wang, Fei; Li, Tun; Thompson-Peer, Katherine L.; Gong, Jiaxin; Murthy, Swetha E.; Coste, Bertrand; Yakubovich, Nikita; Patapoutian, Ardem; Xiang, Yang; Rompolas, Panteleimon; Jan, Yuh Nung

doi:10.1016/j.neuron.2019.01.050

Cited by 147 publications

(159 citation statements)

References 86 publications

(121 reference statements)

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“…Treating human umbilical vein endothelial cells (HUVECs) or prostate cancer cell lines (PC‐3 and LNCaP) with GsMTx4 causes a decrease in cell migration (Li et al, ; Maroto, Kurosky, & Hamill, ) but enhances neurite outgrowth in Xenopus spinal cord explants (Jacques‐Fricke, Seow, Gottlieb, Sachs, & Gomez, ). More recently, Song et al () have shown that Piezo1 activation can inhibit neural regeneration in Drosophila. Here, we show that astrocytes exposed to LPS (to induce Piezo1 expression) and GsMTx4 (to simultaneously block Piezo1 channel opening) migrate faster than astrocytes stimulated with LPS and Yoda1 (which activates Piezo1 channels).…”

Section: Discussionmentioning

confidence: 99%

“…Piezo1 is a nonselective cation channel expressed on the outer cell membrane and is permeable to extracellular calcium (Ca 2+ ) influx (Gottlieb & Sachs, 2012;Li et al, 2015). The calcium-mediated mechanotransduction signaling cascades activated by Piezo1 channel opening are important in a range of developmental and physiological processes including neuronal differentiation (Pathak et al, 2014), axon guidance (Koser et al, 2016), confinement-sensing and cell migration (Hung et al, 2016), neuronal regeneration (Song et al, 2019), shear stress-mediated vasodilation , and immune cell activation (Liu et al, 2018). However, the intracellular molecular mechanisms that underlie Piezo1's role in many of the above cellular processes have yet to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Piezo1 regulates calcium oscillations and cytokine release from astrocytes

Velasco‐Estevez

Rolle

Mampay

et al. 2019

Glia

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Astrocytes are important for information processing in the brain and they achieve this by fine‐tuning neuronal communication via continuous uptake and release of biochemical modulators of neurotransmission and synaptic plasticity. Often overlooked are their important functions in mechanosensation. Indeed, astrocytes can detect pathophysiological changes in the mechanical properties of injured, ageing, or degenerating brain tissue. We have recently shown that astrocytes surrounding mechanically‐stiff amyloid plaques upregulate the mechanosensitive ion channel, Piezo1. Moreover, ageing transgenic Alzheimer's rats harboring a chronic peripheral bacterial infection displayed enhanced Piezo1 expression in amyloid plaque‐reactive astrocytes of the hippocampus and cerebral cortex. Here, we have shown that the bacterial endotoxin, lipopolysaccharide (LPS), also upregulates Piezo1 in primary mouse cortical astrocyte cultures in vitro. Activation of Piezo1, via the small molecule agonist Yoda1, enhanced Ca2+ influx in both control and LPS‐stimulated astrocytes. Moreover, Yoda1 augmented intracellular Ca2+ oscillations but decreased subsequent Ca2+ influx in response to adenosine triphosphate (ATP) stimulation. Neither blocking nor activating Piezo1 affected cell viability. However, LPS‐stimulated astrocyte cultures exposed to the Piezo1 activator, Yoda1, migrated significantly slower than reactive astrocytes treated with the mechanosensitive channel‐blocking peptide, GsMTx4. Furthermore, our data show that activating Piezo1 channels inhibits the release of cytokines and chemokines, such as IL‐1β, TNFα, and fractalkine (CX3CL1), from LPS‐stimulated astrocyte cultures. Taken together, our results suggest that astrocytic Piezo1 upregulation may act to dampen neuroinflammation and could be a useful drug target for neuroinflammatory disorders of the brain.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Piezo1 regulates calcium oscillations and cytokine release from astrocytes

Velasco‐Estevez

Rolle

Mampay

et al. 2019

Glia

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“…Piezo1, the only known homolog of Piezo2, mediates the detection of mechanical force in various cell types inside the body, including interoceptive mechanoreceptors from the nodose ganglion and neurons in the central nervous system (CNS), where it does not encounter significant fluctuations in temperature (18)(19)(20). Piezo1 activation is thought to be triggered primarily by membrane tension (21)(22)(23)(24)(25)(26).…”

mentioning

confidence: 99%

Piezo2 integrates mechanical and thermal cues in vertebrate mechanoreceptors

Wang

Nikolaev

Gracheva

et al. 2019

Proc. Natl. Acad. Sci. U.S.A.

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Tactile information is detected by thermoreceptors and mechanoreceptors in the skin and integrated by the central nervous system to produce the perception of somatosensation. Here we investigate the mechanism by which thermal and mechanical stimuli begin to interact and report that it is achieved by the mechanotransduction apparatus in cutaneous mechanoreceptors. We show that moderate cold potentiates the conversion of mechanical force into excitatory current in all types of mechanoreceptors from mice and tactile-specialist birds. This effect is observed at the level of mechanosensitive Piezo2 channels and can be replicated in heterologous systems using Piezo2 orthologs from different species. The cold sensitivity of Piezo2 is dependent on its blade domains, which render the channel resistant to cold-induced perturbations of the physical properties of the plasma membrane and give rise to a different mechanism of mechanical activation than that of Piezo1. Our data reveal that Piezo2 is an evolutionarily conserved mediator of thermal–tactile integration in cutaneous mechanoreceptors.

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“…The exact roles of Ca 2+ signals in controlling regeneration ranges from promoting to inhibiting regeneration (Chierzi et al, 2005;Enes et al, 2010;Song et al, 2019;Tedeschi et al, 2016). Our results suggest that Ca 2+ spikes promote C3da and C4da neuron regeneration.…”

Section: Ca 2+ Signaling and Axon Regenerationmentioning

confidence: 73%

Gliotransmission orchestrates neuronal type-specific axon regeneration

Ruppell

Wang

et al. 2019

Preprint

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Injured neurons exhibit cell type-specific axon regeneration, but the underlying mechanisms remain elusive. Two subtypes of Drosophila sensory neurons show distinct regenerative competence. Here, we show that axotomy induces long-lasting burst firing and Ca 2+ spikes specifically in the regenerative subtype. Genetic silencing of firing in the regenerative subtype inhibits regeneration. Optogenetic stimulation of the nonregenerative subtype reveals that activity patterns critically determine regeneration; burst firing triggers Ca 2+ spikes and suffices to induce regeneration, while tonic firing fails to induce Ca 2+ spikes and regeneration. We further show the L-type Ca 2+ channel, Dmca1D, regulates Ca 2+ spikes and regeneration. Intriguingly, the regenerative neuronal subtype expresses higher levels of Dmca1D, and overexpression of Dmca1D in the non-regenerative subtype facilitates regeneration. Our studies indicate that injury induces cell type-specific neuronal activities, which act through Ca 2+ spikes to govern regeneration, and suggest that precise control of neuronal activity patterns is an effective way to promote regeneration.

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The Mechanosensitive Ion Channel Piezo Inhibits Axon Regeneration

Cited by 147 publications

References 86 publications

Piezo1 regulates calcium oscillations and cytokine release from astrocytes

Piezo1 regulates calcium oscillations and cytokine release from astrocytes

Piezo2 integrates mechanical and thermal cues in vertebrate mechanoreceptors

Gliotransmission orchestrates neuronal type-specific axon regeneration

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