A Model of the Intracellular Response of an Olfactory Neuron in Caenorhabditis elegans to Odor Stimulation 英文参考文献.docVIP

AModeloftheIntracellularResponseofanOlfactory NeuroninCaenorhabditiseleganstoOdorStimulation MamoruUsuyama1,ChisatoUshida2,3,4,RyuzoShingai1* 1Laboratory ofBioscience,FacultyofEngineering,IwateUniversity,Morioka,Japan, 2TheUnitedGraduateSchoolofAgriculturalSciences,IwateUniversity,Morioka, Japan,3DepartmentofBiochemistryandMolecularBiology,FacultyofAgricultureandLifeScience,HirosakiUniversity,Hirosaki,Japan,4RNAResearchCenter,Hirosaki University,Hirosaki,Japan Abstract Wedevelopedamathematicalmodelofahypotheticalneuronalsignaltransductionpathwaytobetterunderstandolfactory perception in Caenorhabditis elegans. This worm has only three pairs of olfactory receptor neurons. Intracellular Ca decreasesinonepairofolfactoryneuronsinC.elegans,theAWCneurons,followingapplicationofanattractiveodorand 2+ 2+ there is a transient increase in intracellular Ca following removal of odor. The magnitude of this increase is positively correlatedwiththedurationofodorstimulation.Additionally,thisCa2+transientisinducedbyacGMPsecondmessenger system.Weidentifiedlikelycandidatesforthesignaltransductionmoleculesfunctioninginthissystembasedonavailable gene expression and physiological data from AWCs. Our model incorporated a G-protein-coupled odor receptor, a G- protein, a guanylate cyclase as the G-protein effector, and a single phosphodiesterase. Additionally, a cyclic-nucleotide- gated ionchannel andavoltage-gated ionchannel that mediated calcium influx wereincorporated into themodel. We positedthat,uponodorstimulation,guanylatecyclasewassuppressedbytheG-proteinandthat,uponcessationofthe stimulus,theG-protein–inducedsuppressionceasedandcGMPsynthesiswasrestored.Akeyelementofourmodelwasa 2+ Ca -dependent negative feedback loop that ensured that the calcium increases were transient. Two guanylate cyclase- activatingproteinsactedontheeffectorguanylatecyclasetonegativelyregulatecGMPsignalingandtheresultingcalcium influx. Our model was able to closely replicate in silico three important fe