ArticleProceedings of the National Academy of Sciences of the United States of America2007
Yeast gain-of-function mutations reveal structure-function relationships conserved among different subfamilies of transient receptor potential channels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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23 citing papers in PubMed, 40 citations in OpenAlex.
- Structure of the ancient TRPY1 channel from Saccharomyces cerevisiae reveals mechanisms of modulation by lipids and calcium.Structure (London, England : 1993) · 2022Article
- Function and regulation of TRPP2 ion channel revealed by a gain-of-function mutant.Proceedings of the National Academy of Sciences of the United States of America · 2016Article
- Modeling Suggests TRPC3 Hydrogen Bonding and Not Phosphorylation Contributes to the Ataxia Phenotype of the Moonwalker Mouse.Biochemistry · 2015Article
- Comparative sequence analysis suggests a conserved gating mechanism for TRP channels.The Journal of general physiology · 2015Article
- Novel Alleles of gon-2, a C. elegans Ortholog of Mammalian TRPM6 and TRPM7, Obtained by Genetic Reversion Screens.PloS one · 2015Article
- Progressive degeneration of dopaminergic neurons through TRP channel-induced cell death.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Conserved gating elements in TRPC4 and TRPC5 channels.The Journal of biological chemistry · 2013Article
- Molecular bases of multimodal regulation of a fungal transient receptor potential (TRP) channel.The Journal of biological chemistry · 2013Article
- Chimeras reveal a single lipid-interface residue that controls MscL channel kinetics as well as mechanosensitivity.Cell reports · 2013Article
- The core domain as the force sensor of the yeast mechanosensitive TRP channel.The Journal of general physiology · 2011Article
- Multiple modalities converge on a common gate to control K2P channel function.The EMBO journal · 2011Article
- Increased basal activity is a key determinant in the severity of human skeletal dysplasia caused by TRPV4 mutations.PloS one · 2011Article
- Functional and structural studies of TRP channels heterologously expressed in budding yeast.Advances in experimental medicine and biology · 2011Review
- The transient receptor potential family of ion channels.Genome biology · 2011Review
- Forward genetic analysis reveals multiple gating mechanisms of TRPV4.The Journal of biological chemistry · 2010Article
- The tension-transmitting 'clutch' in the mechanosensitive channel MscS.Nature structural & molecular biology · 2010Article
- The use of yeast to understand TRP-channel mechanosensitivity.Pflugers Archiv : European journal of physiology · 2009Review
- Searching for interesting channels: pairing selection and molecular evolution methods to study ion channel structure and function.Molecular bioSystems · 2009Review
- Mechanical force and cytoplasmic Ca(2+) activate yeast TRPY1 in parallel.The Journal of membrane biology · 2009Article
- Multiple unbiased prospective screens identify TRP channels and their conserved gating elements.The Journal of general physiology · 2008Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Transient receptor potential (TRP) channels found in animals, protists, and fungi are primary chemo-, thermo-, or mechanosensors. Current research emphasizes the characteristics of individual channels in each animal TRP subfamily but not the mechanisms common across subfamilies. A forward genetic screen of the TrpY1, the yeast TRP channel, recovered gain-of-function (GOF) mutations with phenotype in vivo and in vitro. Single-channel patch-clamp analyses of these GOF-mutant channels show prominent aberrations in open probability and channel kinetics. These mutations revealed functionally important aromatic amino acid residues in four locations: at the intracellular end of the fifth transmembrane helix (TM5), at both ends of TM6, and at the immediate extension of TM6. These aromatics have counterparts in most TRP subfamilies. The one in TM5 (F380L) aligns precisely with an exceptional Drosophila mutant allele (F550I) that causes constitutive activity in the canonical TRP channel, resulting in rapid and severe retinal degeneration beyond mere loss of phototaxis. Thus, this phenylalanine maintains the balance of various functional states (conformations) of a channel for insect phototransduction as well as one for fungal mechanotransduction. This residue is among a small cluster of phenylalanines found in all known subfamilies of TRP channels. This unique case illustrates that GOF mutations can reveal structure-function principles that can be generalized across different TRP subfamilies. It appears that the conserved aromatics in the four locations have conserved functions in most TRP channels. The possible mechanistic roles of these aromatics and the further use of yeast genetics to dissect TRP channels are discussed.
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