Discrete Dynamics Model for the Speract-Activated Ca2+ Signaling Network Relevant to Sperm Motility 英文参考文献.docVIP

DiscreteDynamicsModelfortheSperact-ActivatedCa2+ SignalingNetworkRelevanttoSpermMotility Jesu′sEspinal1,2,MaximinoAldana1,2,Ada′nGuerrero3,ChristopherWood3,AlbertoDarszon3., 1,2,4 . GustavoMart?′nez-Mekler * 1InstitutodeCienciasFsicas,UniversidadNacionalAuto′nomadeMe′xico,Cuernavaca,Morelos,Me′xico, 2CentrodeCienciasdelaComplejidad,CiudadUniversitaria, Me′xico,Me′xico, 3DepartamentodeGene′ticadelDesarrolloyFisiologaMolecular,InstitutodeBiotecnologa,UniversidadNacionalAuto′nomadeMe′xico, Cuernavaca, Morelos,Me′xico,4CentroInternacionaldeCiencias,Cuernavaca,Morelos,Me′xico Abstract Understanding how spermatozoa approach the egg is a central biological issue. Recently a considerable amount of experimental evidence has accumulated on the relation between oscillations in intracellular calcium ion concentration ([Ca2z]i)intheseaurchinspermflagellum,triggeredbypeptidessecretedfromtheegg,andspermmotility.Determination ofthestructureanddynamicsofthesignalingpathwayleadingtotheseoscillationsisafundamentalproblem.However,a biochemically based formulation for the comprehension of the molecular mechanisms operating in the axoneme as a responsetoexternalstimulusisstilllacking.BasedonexperimentsontheS.purpuratusseaurchinspermatozoa,wepropose a signaling network model where nodes are discrete variables corresponding to the pathway elements and the signal transmissiontakesplaceatdiscretetimeintervalsaccordingtologicalrules.Thevalidityofthismodeliscorroboratedby reproducing previous empirically determined signaling features. Prompted by the model predictions we performed experiments which identified novel characteristics of the signaling pathway. We uncovered the role of a high voltage- activatedCa2zchannelasaregulatorofthedelayintheonsetoffluctuationsafteractivationofthesignalingcascade.This delay time has recently been shown to be an important regulatory factor for sea urchin sperm reorientation. Another findingistheparticipationofavoltage-dependentcalcium-activa