Adaptive selection drives TRPP3 loss-of-function in an Ethiopian population
| العنوان: | Adaptive selection drives TRPP3 loss-of-function in an Ethiopian population |
|---|---|
| المؤلفون: | Mercè Izquierdo-Serra, Jaume Bertranpetit, Sandra Walsh, Albert Edo, José M. Fernández-Fernández, Elena Bosch, Baldo Oliva, Sandra Acosta, Roser Moret, María Lloret |
| المساهمون: | European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Ministerio de Economía y Competitividad (España), Generalitat de Catalunya |
| المصدر: | Digital.CSIC. Repositorio Institucional del CSIC instname Scientific Reports |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | Adult, Male, Patch-Clamp Techniques, Adolescent, Evolution, Molecular biology, Physiology, Population, Biophysics, Fluorescent Antibody Technique, Receptors, Cell Surface, Biology, Polymerase Chain Reaction, Article, Transient receptor potential channel, Young Adult, Loss of Function Mutation, Extracellular, Genetics, Humans, Selection, Genetic, education, Receptor, Loss function, education.field_of_study, Multidisciplinary, Middle Aged, Cell biology, Electrophysiology, Structural biology, Amino Acid Substitution, Taste, Female, Calcium Channels, Ethiopia, Function (biology) |
| الوصف: | TRPP3 (also called PKD2L1) is a nonselective, cation-permeable channel activated by multiple stimuli, including extracellular pH changes. TRPP3 had been considered a candidate for sour sensor in humans, due to its high expression in a subset of tongue receptor cells detecting sour, along with its membership to the TRP channel family known to function as sensory receptors. Here, we describe the functional consequences of two non-synonymous genetic variants (R278Q and R378W) found to be under strong positive selection in an Ethiopian population, the Gumuz. Electrophysiological studies and 3D modelling reveal TRPP3 loss-of-functions produced by both substitutions. R278Q impairs TRPP3 activation after alkalinisation by mislocation of H binding residues at the extracellular polycystin mucolipin domain. R378W dramatically reduces channel activity by altering conformation of the voltage sensor domain and hampering channel transition from closed to open state. Sour sensitivity tests in R278Q/R378W carriers argue against both any involvement of TRPP3 in sour detection and the role of such physiological process in the reported evolutionary positive selection past event. Tis work was funded by the Spanish Ministry of Science and Innovation, the State Research Agency (AEI, Agencia Estatal de Investigación) and FEDER Funds (Fondo Europeo de Desarrollo Regional): Grants BFU2016-77961-P to J.B. and E.B., RTI2018-094809-B-I00 to J.M.F.F., PID2019-110933GB-I00/AEI/10.13039/501100011033 to E.B. and J.B., and CEX2018-000792-M through the “María de Maeztu” Programme for Units of Excellence in R&D to “Departament de Ciències Experimentals i de la Salut”. With the support of Secretaria d’Universitats i Recerca del Departament d’Economia i Coneixement de la Generalitat de Catalunya (GRC 2017 SGR 702). S.W. has had a F.P.I. grant (BES-2014-068994) and M.I.-S. a “Juan de la Cierva-Incorporación” Fellowship funded by the Spanish Ministry of Science and Innovation. |
| وصف الملف: | application/pdf |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::c7a67a5856ddfec01ff650fa5af1728a http://hdl.handle.net/10261/236055 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....c7a67a5856ddfec01ff650fa5af1728a |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |