Scyl1 Regulates Golgi Morphology 英文参考文献.docVIP

Scyl1RegulatesGolgiMorphology JonathonL.Burman¤,JasonN.R.Hamlin,PeterS.McPherson* DepartmentofNeurologyandNeurosurgery,MontrealNeurologicalInstitute,McGillUniversity,Montreal,Quebec,Canada Abstract Background:Membranetraffickingisadefiningfeatureofeukaryoticcells,andisessentialforthemaintenanceoforganelle homeostasis and identity. We previously identified Scy1-like 1 (Scyl1), a member of the Scy1-like family of catalytically inactiveproteinkinases,asahigh-affinitybindingpartnerofCOPIcoats.COPI-coatedvesiclescontrolGolgitoendoplasmic reticulum trafficking and we observed that disruption of Scyl1 function leads to a decrease in trafficking of the KDEL receptorviatheCOPIpathway.WereasonedthatifScyl1playsamajorroleinCOPItraffickingitsdisruptioncouldinfluence Golgihomeostasis. Methodology/PrincipalFindings:WeperformedScyl1knockdowninculturedcellsusingpreviouslyestablishedmethods and observed an alteration in Golgi morphology. Both the surface area and volume of the Golgi is increased in Scyl1- depleted cells, but the continuity and polarity of the organelle is unperturbed. At the ultrastructural level we observe a decreaseintheorderlystructureoftheGolgiwithanincreaseincisternalluminalwidth,whilethenumberofGolgicisternae remains unchanged. The golgin family of proteins forms a detergent resistant network that controls Golgi homeostasis. Disruptionofthisproteinnetworkbyknockdownofthegolginp115disruptstheGolgilocalizationofScyl1.Moreover,we findthatScyl1interactswith58K/formiminotransferasecyclodeaminase(FTCD),aproteinthatistightlyassociatedwiththe cisfaceoftheGolgi. Conclusions/Significance: Our results place Scyl1 at an interface between the golgin network and COPI trafficking and demonstratethatScyl1isrequiredforthemaintenanceofGolgimorphology.Coupledwiththeobservationfromothers thatScyl1isthegeneproductresponsiblefortheneurodegenerativemousemodelmdf,ourresultsadditionallyimplicate theregulationofCOPItraffickingandGolgihomeostasisinneurodegeneration. Citation:BurmanJL,