SarcoEndoplasmic Reticulum Ca2+-ATPases (SERCA) Contribute to GPCR-Mediated Taste Perception 英文参考文献.docVIP

Sarco/EndoplasmicReticulumCa2+-ATPases(SERCA) ContributetoGPCR-MediatedTastePerception NaokoIguchi1,TadahiroOhkuri1,JayP.Slack2,PingZhong2,LiquanHuang1* 1MonellChemicalSensesCenter,Philadelphia,Pennsylvania,UnitedStatesofAmerica,2GivaudanFlavorsCorporation,Cincinnati,Ohio,UnitedStatesofAmerica Abstract The sense of taste is important for providing animals with valuable information about the qualities of food, such as nutritionalorharmfulnature.Mammals,includinghumans,canrecognizeatleastfiveprimarytastequalities:sweet,umami (savory), bitter, sour, and salty. Recent studies have identified molecules and mechanisms underlying the initial steps of 2+ tastant-triggered molecular events in taste bud cells, particularly the requirement of increased cytosolic free Ca concentration ([Ca ]c) for normal taste signal transduction and transmission. Little, however, is known about the 2+ 2+ mechanisms controlling the removal of elevated [Ca ]c from the cytosol of taste receptor cells (TRCs) and how the disruptionofthesemechanismsaffectstasteperception.ToinvestigatethemolecularmechanismofCa clearanceinTRCs, 2+ 2+ we sought the molecules involved in [Ca ]c regulation using a single-taste-cell transcriptome approach. We found that 2+ 2+ into Serca3, a member of the sarco/endoplasmic reticulum Ca -ATPase (SERCA) family that sequesters cytosolic Ca endoplasmic reticulum, is exclusively expressed in sweet/umami/bitter TRCs, which rely on intracellular Ca2+ release for signaling.Serca3-knockout(KO)micedisplayedsignificantlyincreasedaversivebehavioralresponsesandgreatergustatory nerveresponsestobittertastesubstancesbutnottosweetorumamitastesubstances.FurtherstudiesshowedthatSerca2 wasmainlyexpressedintheT1R3-expressingsweetandumamiTRCs,suggestingthatthelossoffunctionofSerca3was possiblycompensatedbySerca2intheseTRCsinthemutantmice.OurdatademonstratethattheSERCAfamilymembers 2+ playanimportantroleintheCa clearanceinTRCsandthatmutationoftheseproteinsmayalterbitterandperhapssweet