TY - JOUR
T1 - Mechanically Activated Ion Channels
AU - Ranade, Sanjeev S.
AU - Syeda, Ruhma
AU - Patapoutian, Ardem
N1 - Funding Information:
Brohawn et al. reported the X-ray crystal structures of TRAAK in conductive and non-conductive conformations ( Brohawn et al., 2014a ). In a non-conductive conformation, a lipid acyl chain density was observed that is proposed to cause an occluded pore. A 5 Å wide lateral opening in the membrane inner leaflet is suggested to be an access window for the lipid acyl chain to enter channel’s cavity. In the conductive conformation, the lipid acyl chain was absent and the presence of Tl + ion led the authors to predict an unhindered and open permeation pathway. The conductive state conformation also showed rotation of TM4 about a central hinge that could presumably block the intra-membrane opening, preventing lipid access to the cavity and permitting ion entry. In a separate study, Lolicato et al. also provide evidence that the TM4 conformational change of TRAAK in a conductive state hinges on a conserved glycine (G268) near the middle of TM4 ( Lolicato et al., 2014 ). The authors report crystal structures of two mutants, G124I and W262S, that render TRAAK channels in an activated state as compared to wild-type. Comparison and superposition of mutants versus wild-type show that straightening of the TM4 helix repositions the TM4 C-terminal end by 23–27 degrees. This large change in TM4 position is also associated with disruption of inter-helical packing between TM2-TM3 transmembrane helices, and an opening of a wide pathway to the inner leaflet of the bilayer. The salient feature of the TRAAK structure by Brohawn et al. is that membrane tension leads to channel activation. This idea is supported by the presence and absence of the ions and lipid-like moiety in the open and closed conformation, respectively. A caveat to the TRAAK structure by Lolicato et al. is that the authors used activating mutations that induce the open conformation. Despite the differences in the models of channel gating, the structural data from both studies identified conformation changes in TM4 of TRAAK channels as a critical component required to favor an open state ( Brohawn et al., 2014a; Lolicato et al., 2014 ).
PY - 2015/9/23
Y1 - 2015/9/23
N2 - Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of touch and hearing, and the unconscious sensation of blood flow. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels. Mechanically activated (MA) ion channels are structurally diverse sensors required for numerous physiological processes including touch, pain, and hearing. Here, Ranade et al. review eukaryotic MA channel families, and explore the potential mechanisms of how these channels might be gated.
AB - Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of touch and hearing, and the unconscious sensation of blood flow. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels. Mechanically activated (MA) ion channels are structurally diverse sensors required for numerous physiological processes including touch, pain, and hearing. Here, Ranade et al. review eukaryotic MA channel families, and explore the potential mechanisms of how these channels might be gated.
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U2 - 10.1016/j.neuron.2015.08.032
DO - 10.1016/j.neuron.2015.08.032
M3 - Review article
C2 - 26402601
AN - SCOPUS:84942134031
VL - 87
SP - 1162
EP - 1179
JO - Neuron
JF - Neuron
SN - 0896-6273
IS - 6
ER -