Biophysical Principles of Ion-Channel-Mediated Mechanosensory Transduction

Cox, Charles D.; Bavi, Navid; Martinac, Boris

doi:10.1016/j.celrep.2019.08.075

Cited by 170 publications

(142 citation statements)

References 172 publications

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“…Certainly, the pattern of Ca 2+ activation in the HFF cells in the vicinity of adhesions is consistent with previous results 22,37,38 , but it is not consistent with the simplistic model of very high membrane tension for the whole cell. Rather, there appear to be local activation events that involve elements from the adhesions that may alter local membrane tension/curvature or the association of membrane/cytoskeletal proteins that can modulate the mechanical gating of Piezo1 activity [39][40][41] .…”

Section: Discussionmentioning

confidence: 99%

“…The fact that stretch-dependent Ca 2+ accumulation is blocked by calpain inhibition further indicates that Piezo1 contributes to initial Ca 2+ release but calpain cleavage enables the higher levels of Ca 2+ entry that drive apoptosis 26 . Although Piezo1 appears in many different mechanical functions, the activation mechanism of Piezo1 is complex and both contributions from membrane tension and interaction with cytoskeletal proteins may modulate its activity 39,43 .…”

Section: Discussionmentioning

confidence: 99%

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Force-dependent recruitment of Piezo1 drives adhesion maturation and calcium entry in normal but not tumor cells

Yao

Tijore

Cox

et al. 2020

Preprint

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Piezo1 is a mechanosensitive Ca 2+ -permeable channel that has been implicated in a number of mechanosensing processes. It is diffusive on plasma membranes and activated by local membrane tension changes yet recent data suggest that Piezo1 activity is tightly coupled to the integrin-mediated actin cytoskeleton through a poorly understood mechanism. In our studies, we found that Piezo1 stably localizes to RGD matrix adhesions in normal but not in transformed cells. Piezo1 binding requires contractility and triggers local Ca 2+ entry during adhesion formation and turnover. In transformed cells, Piezo1 level does not affect adhesion morphology; and there is no detectable Ca 2+ influx around adhesions. Based upon these findings, we suggest that Piezo1 is a novel component of integrin-based adhesions in non-transformed cells and contributes to the distinct mechanosensing and Ca 2+ signaling in normal vs transformed cells.Concentration of Piezo1 at adhesions is a key factor underlying Piezo1's physiological functions.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Force-dependent recruitment of Piezo1 drives adhesion maturation and calcium entry in normal but not tumor cells

Yao

Tijore

Cox

et al. 2020

Preprint

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“…Among the suggested TRP channels, there is substantial evidence of TRPA1 being involved in mechanical sensory stimulation, and especially in noxious mechanotransduction e.g., related to nerve-injury, inflammation and anti-cancer treatment (5,6). However, it still remains to be demonstrated that TRPA1 exhibit mechanosensitivity in the absence of extra-and intra cellular components (3,5,13).…”

Section: Discussionmentioning

confidence: 99%

Human TRPA1 is an inherently mechanosensitive bilayer-gated ion channel

Moparthi

Zygmunt

2020

Preprint

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The Transient Receptor Potential Ankyrin 1 (TRPA1) channel is an intrinsic chemo-and thermo-sensitive ion channel with distinct sensory signaling properties. Although a role of TRPA1 in mammalian mechanosensory transduction in vivo seems likely, it remains to be shown that TRPA1 has the inherent capability to respond to mechanical stimuli. Here we have used the patch-clamp technique to study the response of human purified TRPA1 (hTRPA1), reconstituted into artificial lipid bilayers, to changes in bilayer pressure. We report that hTRPA1 responded with increased single-channel open probability (Po) within the applied pressure interval of 7.5 to 60 mmHg with a half maximum Po (P50) value of 38.0 ± 2.3 mmHg. The Po value reached a maximum close to 1 (0.87 ± 0.02) at 60 mmHg. Within the same pressure interval, hTRPA1 without its N-terminal ankyrin repeat domain (Δ1-688 hTRPA1) responded fully opened (0.99 ± 0.01) at 60 mmHg and with a P50 value of 39.0 ± 1.1 mmHg. The pressure-evoked responses of hTRPA1 and Δ1-688 hTRPA1 at 45 mmHg were inhibited by the TRPA1 antagonist HC030031, and the activity of purified hTRPA1 at 45 mmHg was abolished by the thiol reducing agent tris(2-carboxyethyl)phosphine (TCEP). In conclusion, hTRPA1 is an inherent mechanosensitive ion channel gated by force-from-lipids. The hTRPA1 mechanosensitivity is dependent on the redox environment, and it is suggested that oxidative stress shifts hTRPA1 into a protein conformation sensitive to mechanical stimuli.

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“…Further to this point, it is important to note that even homologues of the prototypical mechanosensitive channel MscL exhibit a different sensitivity to membrane stretch and curvature, despite their high degree of sequence similarity (Mukherjee et al, 2014). Thus, it is eminently feasible that channel structure influences stretch and curvature sensitivity of an ion channel (Cox et al, 2019).…”

Section: Coreymentioning

confidence: 99%

Mammalian TRP ion channels are insensitive to membrane stretch

Nikolaev

Cox

Ridone

et al. 2019

Journal of Cell Science

130

105

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TRP channels of the transient receptor potential ion channel superfamily are involved in a wide variety of mechanosensory processes, including touch sensation, pain, blood pressure regulation, bone loading and detection of cerebrospinal fluid flow. However, in many instances it is unclear whether TRP channels are the primary transducers of mechanical force in these processes. In this study, we tested stretch activation of eleven TRP channels from six mammalian subfamilies. We found that these TRP channels were insensitive to short membrane stretches in cellular systems. Furthermore, we purified TRPC6 and demonstrated its insensitivity to stretch in liposomes, an artificial bilayer system free from cellular components. Additionally, we demonstrated that, when expressed in C. elegans neurons, mouse TRPC6 restores the mechanoresponse of a touch insensitive mutant but requires diacylglycerol for activation. These results strongly suggest that the mammalian members of the TRP ion channel family are insensitive to tension induced by cell membrane stretching and, thus, are more likely to be activated by cytoplasmic tethers or downstream components and to act as amplifiers of cellular mechanosensory signaling cascades.

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Biophysical Principles of Ion-Channel-Mediated Mechanosensory Transduction

Cited by 170 publications

References 172 publications

Force-dependent recruitment of Piezo1 drives adhesion maturation and calcium entry in normal but not tumor cells

Force-dependent recruitment of Piezo1 drives adhesion maturation and calcium entry in normal but not tumor cells

Human TRPA1 is an inherently mechanosensitive bilayer-gated ion channel

Mammalian TRP ion channels are insensitive to membrane stretch

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