Mechanosensitive ion channel
Mechanosensitive channels (MS channels) are ion channels found in a number of tissues and organisms and are thought to be the sensors for a number of systems including the senses of touch, hearing and balance, as well as participating in cardiovascular regulation and osmotic homeostasis (e.g. thirst). They are present in the membranes of organisms from the three domains of life: bacteria, archaea, and eukarya. Mechanosensitive channels were first observed in chick skeletal muscles by Falguni Guharay and Frederick Sachs in 1983 and the results were published in 1984.
For a protein to be considered mechanosensitive, it must respond to a mechanical deformation of the membrane. Mechanical deformations can include changes in the tension, thickness, or curvature of the membrane. Mechanosensitive channels respond to membrane tension by altering their conformation between an open state and a closed state. One type of mechanically sensitive ion channel activates specialized sensory cells, such as cochlear hair cells and some touch sensory neurons, in response to forces applied to proteins.
Recently, a new mechanosensitive ion channel family was cloned, with two mammalian members, PIEZO1 and PIEZO2. Both these channels are expressed in the lungs and bladder, organs with important mechanosensory functions. Piezo1 is also expressed in the skin, and in red blood cells, and its gain of function mutations cause hereditary xerocytosis. Piezo2 is expressed in sensory neurons of the dorsal root and trigeminal ganglia indicating that it may play a role in touch sensation. Mutations in piezo2 are associated with a human disease named Distal Arthrogryposis.
The bacterial MS channels are the best studied, and provide a paradigm of how a protein senses membrane stretch. They are involved in osmotic homeostasis, serving as 'emergency release valves' protecting the cell from acute decreases in osmotic environment. There are two families of bacterial MS channels:
- Large-conductance mechanosensitive channel, MscL
- Small-conductance mechanosensitive channels (MscS or YggB). The pressure threshold for MscS opening is 50% that of MscL.
The MscS family is much larger and more variable in size and sequence than the MscL family. Much of the diversity in MscS proteins occurs in the size of the transmembrane regions, which ranges from three to eleven transmembrane helices, although the three C-terminal helices are conserved.
MscS folds as a homo-heptamer with a cylindrical shape, and can be divided into transmembrane and extramembrane regions: an N-terminal periplasmic region, a transmembrane region, and a C-terminal cytoplasmic region (middle and C-terminal domains). The transmembrane region forms a channel through the membrane that opens into a chamber enclosed by the extramembrane portion, the latter connecting to the cytoplasm through distinct portals.
- Pivetti CD, Yen MR, Miller S, Busch W, Tseng YH, Booth IR, Saier MH (March 2003). "Two families of mechanosensitive channel proteins". Microbiol. Mol. Biol. Rev. 67 (1): 66–85, table of contents. doi:10.1128/MMBR.67.1.66-85.2003. PMC 150521. PMID 12626684.
- Guharay F, Sachs F (July 1984). "Stretch-activated single ion channel currents in tissue-cultured embryonic chick skeletal muscle". J. Physiol. (Lond.) 352: 685–701. doi:10.1113/jphysiol.1984.sp015317. PMC 1193237. PMID 6086918.
- Sukharev SI, Martinac B, Arshavsky VY, Kung C (July 1993). "Two types of mechanosensitive channels in the Escherichia coli cell envelope: solubilization and functional reconstitution". Biophys. J. 65 (1): 177–83. doi:10.1016/S0006-3495(93)81044-0. PMC 1225713. PMID 7690260.
- Haswell ES, Phillips R, Rees DC (October 2011). "Mechanosensitive channels: what can they do and how do they do it?". Structure 19 (10): 1356–69. doi:10.1016/j.str.2011.09.005. PMC 3203646. PMID 22000509.
- Ernstrom GG, Chalfie M (2002). "Genetics of sensory mechanotransduction". Annu. Rev. Genet. 36: 411–53. doi:10.1146/annurev.genet.36.061802.101708. PMID 12429699.
- García-Añoveros J, Corey DP (May 1996). "Touch at the molecular level. Mechanosensation". Curr. Biol. 6 (5): 541–3. doi:10.1016/S0960-9822(02)00537-7. PMID 8805263.
- Coste B, Mathur J, Schmidt M, Earley TJ, Ranade S, Petrus MJ, Dubin AE, Patapoutian A (October 2010). "Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels". Science 330 (6000): 55–60. doi:10.1126/science.1193270. PMC 3062430. PMID 20813920.
- Zarychanski R, Schulz VP, Houston BL, Maksimova Y, Houston DS, Smith B, Rinehart J, Gallagher PG (August 2012). "Mutations in the mechanotransduction protein PIEZO1 are associated with hereditary xerocytosis". Blood 120 (9): 1908–15. doi:10.1182/blood-2012-04-422253. PMID 22529292.
- Coste B, Houge G, Murray MF, Stitziel N, Bandell M, Giovanni MA, Philippakis A, Hoischen A, Riemer G, Steen U, Steen VM, Mathur J, Cox J, Lebo M, Rehm H, Weiss ST, Wood JN, Maas RL, Sunyaev SR, Patapoutian A (March 2013). "Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis". Proc. Natl. Acad. Sci. U.S.A. 110 (12): 4667–72. doi:10.1073/pnas.1221400110. PMC 3607045. PMID 23487782.
- Bass RB, Strop P, Barclay M, Rees DC (November 2002). "Crystal structure of Escherichia coli MscS, a voltage-modulated and mechanosensitive channel". Science 298 (5598): 1582–7. doi:10.1126/science.1077945. PMID 12446901.