BB48CH20_RosenARjats.clsMarch28,201912:21AnnualReviewofBiophysicsRegulationofTransmembraneSignalingbyPhaseSeparationLindsayB.Case,JonathonA.Ditlev,andMichaelK.RosenDepartmentofBiophysicsandHowardHughesMedicalInstitute,UniversityofTexasSouthwesternMedicalCenter,Dallas,Texas75390,USA;email:lindsay.case@utsouthwestern.edu,jonathon.ditlev@utsouthwestern.edu,michael.rosen@utsouthwestern.eduAnnu.Rev.Biophys.2019.48:465–94TheAnnualReviewofBiophysicsisonlineatbiophys.annualreviews.orghttps://doi.org/10.1146/annurev-biophys-052118-115534Copyright©2019byAnnualReviews.AllrightsreservedKeywordsphaseseparation,receptororganization,cellsignaling,receptorclusters,biomolecularcondensatesAbstractCellsurfacetransmembranereceptorsoftenformnanometer-tomicrometer-scaleclusterstoinitiatesignaltransductioninresponsetoenvironmentalcues.Extracellularligandoligomerization,domain-domaininteractions,andbindingtomultivalentproteinsallcontributetoclusterformation.Herewereviewthecurrentunderstandingofmechanismsdrivingclusterformationinaseriesofrepresentativereceptorsystems:glycosylatedreceptors,immunereceptors,celladhesionreceptors,Wntreceptors,andreceptortyrosinekinases.Wesuggestthattheseclusterssharepropertiesofsystemsthatundergoliquid–liquidphaseseparationandcouldbeinvestigatedinthislight.465ReviewinAdvancefirstpostedonApril5,2019.(Changesmaystilloccurbeforefinalpublication.)Annu.Rev.Biophys.2019.48.Downloadedfromwww.annualreviews.orgAccessprovidedbyColumbiaUniversityon04/06/19.Forpersonaluseonly.BB48CH20_RosenARjats.clsMarch28,201912:21ContentsINTRODUCTION..............................................................466COUPLEDOLIGOMERIZATIONANDPHASESEPARATION................467ABriefIntroductiontoPhaseSeparation........................................467OligomerizationCanBeCoupledtoPhaseSeparationinMultivalentProteins.....468DimensionalityConsiderations..................................................470CARBOHYDRATE–LECTININTERACTIONSINRECEPTOROLIGOMERIZATION.............................
