Functional and Spatial Analysis of C. elegans SYG-1 and SYG-2, Orthologs of the NephNephrin Cell Adhesion Module Directing Selective Synaptogenesis 英文参考文献.docVIP

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Functional and Spatial Analysis of C. elegans SYG-1 and SYG-2, Orthologs of the NephNephrin Cell Adhesion Module Directing Selective Synaptogenesis 英文参考文献.doc

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Functional and Spatial Analysis of C. elegans SYG-1 and SYG-2, Orthologs of the NephNephrin Cell Adhesion Module Directing Selective Synaptogenesis 英文参考文献

FunctionalandSpatialAnalysisofC.elegansSYG-1and SYG-2,OrthologsoftheNeph/NephrinCellAdhesion ModuleDirectingSelectiveSynaptogenesis NicolaWanner1,5,FoteiniNoutsou1,RalfBaumeister2,3,4,GerdWalz1,4,TobiasB.Huber1,4,5*. ,Elke Neumann-Haefelin1*. 1RenalDivision, UniversityHospitalFreiburg,Freiburg,Germany, 2BioinformaticsandMolecularGenetics(FacultyofBiology)andZBMZCenterforBiochemistryand MolecularMedicine(FacultyofMedicine),Albert-Ludwigs-Universita¨t Freiburg,Freiburg,Germany,3FRIASSchoolofLifeSciences(LIFENET),Albert-Ludwigs-Universita¨t Freiburg,Freiburg,Germany, 4CentreforBiologicalSignallingStudies (bioss), Albert-Ludwigs-Universita¨t Freiburg,Freiburg,Germany,5Spemann Graduate Schoolof BiologyandMedicine,UniversityofFreiburg,Freiburg,Germany Abstract The assembly of specific synaptic connections represents a prime example of cellular recognition. Members of the Ig superfamily are among the most ancient proteins represented in the genomes of both mammalian and invertebrate organisms, where they constitute a trans-synaptic adhesion system. The correct connectivity patterns of the highly conserved immunoglobulin superfamily proteins nephrin and Neph1 are crucial for the assembly of functional neuronal circuitsandtheformationofthekidneyslitdiaphragm,asynapse-likestructureformingthefiltrationbarrier.Here,weutilize thenematodeC.elegansmodelforstudyingtherequirementsofsynapticspecificitymediatedbynephrin-Nephproteins.In C. elegans, the nephrin/Neph1 orthologs SYG-2 and SYG-1 form intercellular contacts strictly in trans between epithelial guidepost cells andneurons specifying the localizationof synapses. Wedemonstrate afunctionalconservationbetween mammalian nephrin and SYG-2. Expression of nephrin effectively compensated loss of syg-2 function in C. elegans and restoreddefectivesynapticconnectivityfurtherestablishingtheC.eleganssystemasavaluablemodelforslitdiaphragm proteins. Next, we investigated the effect of SYG-1 and SYG-2 trans homodimerization respect