Seeonlineversionforlegendandreferences.SnapShot:Endosome-to-GolgiRetrievalMatthewN.J.SeamanCambridgeInstituteforMedicalResearch,Cambridge,CB20XY,UKSeeonlineversionforlegendandreferences.1198Cell139,December11,2009©2009ElsevierInc.DOI10.1016/j.cell.2009.11.040SnapShot:Endosome-to-GolgiRetrievalMatthewN.J.SeamanCambridgeInstituteforMedicalResearch,Cambridge,CB20XY,UK1198.e1Cell139,December11,2009©2009ElsevierInc.DOI10.1016/j.cell.2009.11.040Theendosome-to-Golgiretrievalpathwayregulatesthelocalizationofmanyimportantmembraneproteins,ishighlyconservedineukaryotes,andrepresentsakeypointofintersectionofthesecretoryandendocyticpathways.Endosome-to-Golgitransportplaysaroleindiverseprocessessuchaslysosomebiogenesis,transcytosis,Wntsignaling,andamyloidprecursorproteinlocalizationandprocessing.Thebestcharacterized“cargo”intheendosome-to-Golgipathwayinmammalsisthecation-independentmannose6-phosphatereceptor(CIMPR)thatmediatessortingoflysosomalhydrolasesintoclathrin-coatedvesiclesattheGolgi/trans-Golginetwork(TGN).Endosome-to-Golgiretrievalessentiallycomprisesthreediscretestepsinvolving(1)cargoselection,(2)tubuleformationandtransport,and(3)tethering/dockingattheGolgi/TGN;thepictureiscomplicated,however,byevidenceofatleasttwoendosome-to-Golgiretrievalpathwaysthatmayfunctioninseriesorinparallel.Thethreestepsareshowninthefigurealongwithsomeofthekeymachineryrequiredforeachstep.Studiesinyeast(Saccharomycescerevisiae)andmammaliancellshaveidentifiedmuchofthecoremachinerythatmediatesendosome-to-Golgiretrievalandhaverevealedmechanisticsimilaritieswithothermembranetraffickingpathways.Inyeast,fiveproteins,Vps5p,Vps17p,Vps26p,Vps29p,andVps35p,assembleintotheretromercomplexandlocalizetoendosomalmembranestomediateendosome-to-Golgiretrievalofthevacuolarhydrolasereceptor,Vps10p.Retromercanbebiochemicallydissectedintotwosubcomplexes:thecargo-selectiveVps35p/Vps29p/Vps26psubcomplexandthesortingnexin(Snx)subcomplexcomprisingVps5p/Vps17pinyeast.Inmammals,theVps35,Vps29,andVps26proteinsformast...