While we usually take sensations such as pain, warmth, or cold for granted, the molecules involved in these processes orchestrate a complex biological response to the outside world and remain almost a complete mystery. The sense of touch consists of the perception of multiple discrete types of thermal, mechanical, and chemical stimuli. A great deal remains unknown about the genes involved in sensing these stimuli. With the completion of the human genome project, we have powerful new methods to identify these elusive sensory molecules. Using such tools, we recently cloned the first gene involved in our ability to sense cold temperatures. Trpm8, encodes for a protein present at the plasma membrane of cold-sensing neurons that belongs to the Transient Receptor Potential (TRP) channel family. More recently, we have identified a novel sensory channel that responds to colder temperatures, ANKTM1. ANTKM1 is distantly related to TRPM8 and is one of six TRP family members to sense temperature. The cold-activated TRP channels allow positive charged ions into the cell as the external temperature reaches a critical threshold. We wish to understand much more about this activation process. Most fundamentally, how do these channels actually sense cold temperature at the molecular level? TRP channels may respond to thermal stimuli using completely novel mechanisms than those involved in classical ligand-gated channels. Finally, we will ask if these channels are required for cold detection and pain sensation in-vivo. ? ?
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| Kim, Sung Eun; Patapoutian, Ardem; Grandl, Jörg (2013) Single residues in the outer pore of TRPV1 and TRPV3 have temperature-dependent conformations. PLoS One 8:e59593 |
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| Grandl, Jorg; Kim, Sung Eun; Uzzell, Valerie et al. (2010) Temperature-induced opening of TRPV1 ion channel is stabilized by the pore domain. Nat Neurosci 13:708-14 |
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| Hu, Hongzhen; Bandell, Michael; Petrus, Matt J et al. (2009) Zinc activates damage-sensing TRPA1 ion channels. Nat Chem Biol 5:183-90 |
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