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.

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Figures

Figure 1

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

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).

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