ReviewPhaseSeparationinMembraneBiology:TheInterplaybetweenMembrane-BoundOrganellesandMembranelessCondensatesYanG.Zhao1andHongZhang2,3,*1DepartmentofMolecular,CellandCancerBiology,UniversityofMassachusettsMedicalSchool,Worcester,MA01605,USA2NationalLaboratoryofBiomacromolecules,CASCenterforExcellenceinBiomacromolecules,InstituteofBiophysics,ChineseAcademyofSciences,Beijing100101,China3CollegeofLifeSciences,UniversityofChineseAcademyofSciences,Beijing100049,China*Correspondence:hongzhang@ibp.ac.cnhttps://doi.org/10.1016/j.devcel.2020.06.033Ineukaryoticcells,variousmembrane-boundorganellescompartmentalizediversecellularactivitiesinaspatiallyandtemporallycontrolledmanner.Numerousmembranelessorganellesassembledvialiquid-liquidphaseseparation(LLPS),knownascondensates,alsofacilitatecompartmentalizationofcellularfunctions.Emergingevidenceshowsthatthesetwoorganelletypesinteractinmanybiologicalprocesses.Membranesmodulatethebiogenesisanddynamicsofphase-separatedcondensatesbyservingasassemblyplatformsorbyformingdirectcontacts.Phaseseparationofmembrane-associatedproteinsparticipatesinvarioustraffickingevents,suchasclusteringofvesiclesfortemporallycontrolledfusionandstorage,andtransportofmembranelesscondensatesonmembrane-boundorganelles.Phaseseparationalsoactsincargotraf-fickingpathwaysbysortinganddockingcargosfortranslocon-mediatedtransportacrossmembranes,byshuttlingcargosthroughthenuclearporecomplex,andbytriggeringtheformationofsurroundingautopha-gosomesfordeliverytolysosomes.Thecoordinatedactionsofmembrane-boundandmembranelessorgan-ellesensurespatiotemporalcontrolofvariouscellularfunctions.IntroductionEukaryoticcellsarecompartmentalizedbymembrane-boundor-ganellestoensurethatspecificbiochemicalreactionsandcellularfunctionsoccurinaspatiallyrestrictedmanner.Themembranesoftheseorganelleshaveuniqueidentities.Forexample,thedistinctidentitiesoftheendomembranesystem(theendoplasmicreticulum[ER],Golgi,endosomes,andlysosomes)areinpartspecifiedbydifferentialenrichmentofRABGTPasesandpho...
