How ion channels sense mechanical force: insights from mechanosensitive K2P channels TRAAK, TREK1, and TREK2.
The ability to sense and respond to mechanical forces is essential for life and cells have evolved a variety of systems to convert physical forces into cellular signals. Within this repertoire are the mechanosensitive ion channels, proteins that play critical roles in mechanosensation by transducing forces into ionic currents across cellular membranes. Understanding how these channels work, particularly in animals, remains a major focus of study. Here, I review the current understanding of force gating for a family of metazoan mechanosensitive ion channels, the two-pore domain K(+) channels (K2Ps) TRAAK, TREK1, and TREK2. Structural and functional insights have led to a physical model for mechanical activation of these channels. This model of force sensation by K2Ps is compared to force sensation by bacterial mechanosensitive ion channels MscL and MscS to highlight principles shared among these evolutionarily unrelated channels, as well as differences of potential functional relevance. Recent advances address fundamental questions and stimulate new ideas about these unique mechanosensors.
Laboratory of Molecular Neurobiology and Biophysics and Howard Hughes Medical Institute, The Rockefeller University, New York, New York.
Stephen G
SG
Brohawn
D000818:Animals; D006801:Humans; D015640:Ion Channel Gating / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008956:Models, Chemical; D015221:Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D024683:Potassium Channels, Tandem Pore Domain / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
C503438:KCNK10 protein, human; C503432:KCNK4 protein, human; D015221:Potassium Channels; D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1
TRAAK; TREK1; TREK2; ion channel gating; mechanosensation; membrane tension