Forcing open TRP channels: Mechanical gating as a unifying activation mechanism - PubMed (original) (raw)
Review
Forcing open TRP channels: Mechanical gating as a unifying activation mechanism
Chao Liu et al. Biochem Biophys Res Commun. 2015.
Abstract
Transient receptor potential (TRP) proteins are cation channels that comprise a superfamily of molecular sensors that enable animals to detect a wide variety of environmental stimuli. This versatility enables vertebrate and invertebrate TRP channels to function in a diversity of senses, ranging from vision to taste, smell, touch, hearing, proprioception and thermosensation. Moreover, many individual TRP channels are activated through a surprising range of sensory stimuli. The multitasking nature of TRP channels raises the question as to whether seemingly disparate activators gate TRPs through common strategies. In this regard, a recent major advance is the discovery that a phospholipase C (PLC)-dependent signaling cascade activates the TRP channels in Drosophila photoreceptor cells through generation of force in the lipid-bilayer. The premise of this review is that mechanical force is a unifying, common strategy for gating TRP channels. In addition to several TRP channels that function in mechanosensation and are gated by force applied to the cells, changes in temperature or alterations in the concentration of lipophilic second messengers through stimulation of signaling cascades, cause architectural modifications of the cell membrane, which in turn activate TRP channels through mechanical force. Consequently, TRPs are capable of functioning as stretch-activated channels, even in cases in which the stimuli that initiate the signaling cascades are not mechanical. We propose that most TRPs are actually mechanosensitive channels (MSCs), which undergo conformational changes in response to tension imposed on the lipid bilayer, resulting in channel gating.
Keywords: Mechanical gating; Mechanosensitive channels; PLC-dependent signaling; TRP channel.
Copyright © 2015 Elsevier Inc. All rights reserved.
Figures
Figure 1
Model of direct force-activation of TRP channels without a signaling cascade. (A) The TRP channel is closed prior to the mechanical stimulus. (B) The TRP channel opens in response to application of external force to the plasma membrane and/or the TRP channel. No signaling cascade is involved in this process.
Figure 2
Model of direct activation of TRP channels by force generated via a signaling cascade. (A) TRP channel is closed before the stimulus. (B) TRP channel is opened following activation of a the signaling cascade: 1) a stimulus, such as light or a chemical agonist, activates the GPCR, 2) the heterotrimeric G-protein (Gq) engages the GPCR, resulting in exchange of GTP for GDP, and dissociation of the βγ from the Gqα subunit, 3) PLC is stimulated by interaction with Gqα-GTP, resulting in the hydrolysis of PIP2 and production of IP3, DAG and H+, 4) the membrane stretches due to cleavage of the head group (DAG) from PIP2, and 5) membrane-deformation activates the TRP channel, leading to influx of cations. We also propose that hydrolysis of PIP2 through engagement of an RTK and stimulation of PLCγ1, leads to stretch-activation of TRP channels (not shown).
Similar articles
- TRPs in mechanosensing and volume regulation.
Plant TD. Plant TD. Handb Exp Pharmacol. 2014;223:743-66. doi: 10.1007/978-3-319-05161-1_2. Handb Exp Pharmacol. 2014. PMID: 24961968 Review. - TRP channels in mechanosensation: direct or indirect activation?
Christensen AP, Corey DP. Christensen AP, et al. Nat Rev Neurosci. 2007 Jul;8(7):510-21. doi: 10.1038/nrn2149. Nat Rev Neurosci. 2007. PMID: 17585304 Review. - Voltage sensing in thermo-TRP channels.
Brauchi S, Orio P. Brauchi S, et al. Adv Exp Med Biol. 2011;704:517-30. doi: 10.1007/978-94-007-0265-3_28. Adv Exp Med Biol. 2011. PMID: 21290314 Review. - The TRP superfamily of cation channels.
Montell C. Montell C. Sci STKE. 2005 Feb 22;2005(272):re3. doi: 10.1126/stke.2722005re3. Sci STKE. 2005. PMID: 15728426 Review. - C. elegans TRP family protein TRP-4 is a pore-forming subunit of a native mechanotransduction channel.
Kang L, Gao J, Schafer WR, Xie Z, Xu XZ. Kang L, et al. Neuron. 2010 Aug 12;67(3):381-91. doi: 10.1016/j.neuron.2010.06.032. Neuron. 2010. PMID: 20696377 Free PMC article.
Cited by
- Roles of the ocular pressure, pressure-sensitive ion channel, and elasticity in pressure-induced retinal diseases.
Pang JJ. Pang JJ. Neural Regen Res. 2021 Jan;16(1):68-72. doi: 10.4103/1673-5374.286953. Neural Regen Res. 2021. PMID: 32788449 Free PMC article. - The Role of Physical Stimuli on Calcium Channels in Chondrogenic Differentiation of Mesenchymal Stem Cells.
Uzieliene I, Bernotas P, Mobasheri A, Bernotiene E. Uzieliene I, et al. Int J Mol Sci. 2018 Oct 1;19(10):2998. doi: 10.3390/ijms19102998. Int J Mol Sci. 2018. PMID: 30275359 Free PMC article. Review. - Channelling the Force to Reprogram the Matrix: Mechanosensitive Ion Channels in Cardiac Fibroblasts.
Stewart L, Turner NA. Stewart L, et al. Cells. 2021 Apr 23;10(5):990. doi: 10.3390/cells10050990. Cells. 2021. PMID: 33922466 Free PMC article. Review. - Mechanosensitive ion channels in cell migration.
Canales Coutiño B, Mayor R. Canales Coutiño B, et al. Cells Dev. 2021 Jun;166:203683. doi: 10.1016/j.cdev.2021.203683. Epub 2021 Apr 27. Cells Dev. 2021. PMID: 33994356 Free PMC article. Review. - Use the force, fluke: Ligand-independent gating of Schistosoma mansoni ion channel TRPMPZQ.
Chulkov EG, Isaeva E, Stucky CL, Marchant JS. Chulkov EG, et al. Int J Parasitol. 2023 Jul;53(8):427-434. doi: 10.1016/j.ijpara.2022.11.004. Epub 2023 Jan 4. Int J Parasitol. 2023. PMID: 36610555 Free PMC article.
References
- Montell C, Jones K, Hafen E, Rubin G. Rescue of the Drosophila phototransduction mutation trp by germline transformation. Science. 1985;230:1040–1043. - PubMed
- Montell C, Rubin GM. Molecular characterization of the Drosophila trp locus: a putative integral membrane protein required for phototransduction. Neuron. 1989;2:1313–1323. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- R01 DC007864/DC/NIDCD NIH HHS/United States
- EY10852/EY/NEI NIH HHS/United States
- R01 EY010852/EY/NEI NIH HHS/United States
- DC007864/DC/NIDCD NIH HHS/United States
- R01 EY008117/EY/NEI NIH HHS/United States
- EY08117/EY/NEI NIH HHS/United States
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases