最新考研资料：细胞生物学六章基质与内膜(中)课件

考研资料：北京大学细胞生物学第六章基质与内膜(中)考研资料：北京大学细胞生物学第六章基质与内膜(中)4.ThestructureandfunctionsofLysosomesA.CharacteristicsofLysosomes①Lysosomeisaheterogenousorganelle:PrimarylysosomesSecondlysosomesheterophagicautophagicResidualbodyPrimaryLys.SecondLys4.Thestructureandfunctions2最新考研资料：细胞生物学六章基质与内膜(中)课件3最新考研资料：细胞生物学六章基质与内膜(中)课件4最新考研资料：细胞生物学六章基质与内膜(中)课件5最新考研资料：细胞生物学六章基质与内膜(中)课件6最新考研资料：细胞生物学六章基质与内膜(中)课件7最新考研资料：细胞生物学六章基质与内膜(中)课件8表1.神经鞘脂贮积病疾病缺失酶类主要贮积底物后果GM1神经节苷脂贮积症GM1-半乳糖苷酶神经节苷脂GM1智力迟钝，肝脏肥大，骨骼受累，2岁前死亡泰－萨二氏病己糖胺酶A神经节苷脂GM2智力迟钝，失明，3岁前死亡法布莱氏病-半乳糖苷酶A三己糖神经酰胺皮疹，肾功能丧失，下肢疼痛山霍夫氏病己糖胺酶A和B神经节苷脂GM2和红细胞糖苷酯与泰－萨氏疾病症状相似，但发展更快高歇氏病葡糖脑苷酯酶葡糖脑苷脂肝脏和脾脏肿大，长骨腐蚀，只在婴儿期发生智力迟钝尼-皮二氏病鞘磷脂水解酶鞘磷脂肝脏和脾脏肿大，智力迟钝Farber’s脂肪肉芽肿病神经酰胺水解酶神经酰胺疼痛性与退行性的关节变形，皮肤瘤，几年内死亡Krabbe’s病半乳糖脑苷酯酶半乳糖脑苷脂髓磷脂缺失，智力迟钝，2岁前死亡脑硫脂沉积芳基硫酸酯酶脑硫脂智力迟钝，前十年死亡表1.神经鞘脂贮积病疾病缺失酶类主要贮积底物后果GM1神经9D.BiogenesisofLysosomesFigure

6-23

Thetransportofnewlysynthesizedlysosomalhydrolasestolysosomes.

Theprecursorsoflysosomalhydrolasesarecovalentlymodifiedbytheadditionofmannose6-phosphateintheCGN.TheythenbecomesegregatedfromallothertypesofproteinsintheTGNbecauseaspecificclassoftransportvesiclesbuddingfromtheTGNconcentratesmannose6-phosphate-specificreceptors,whichbindthemodifiedlysosomalhydrolases.Thesevesiclessubsequentlyfusewithlateendosomes.AtthelowpHofthelateendosomethehydrolasesdissociatefromthereceptors,whicharerecycledtotheGolgiapparatusforfurtherroundsoftransport.Inlateendosomesthephosphateisremovedfromthemannoseonthehydrolases,furtherensuringthatthehydrolasesdonotreturntotheGolgiapparatuswiththereceptor.D.BiogenesisofLysosomesFig10Mannose6-phosphateresiduestargetproteinstolysosomesTargetingofsolublelysosomalenzymestoendosomesandlysosomesbyM-6-PtagMannose6-phosphateresiduest11PhosphorylationofmannoseresiduesonlysosomalenzymescatalyzedbytwoenzymesRecognitionsitebindstoSignalpatchGlcNAcphosphotransferasephosphodiesterasePhosphorylationofmannose12Figure6-40.Themannose6-phosphate(M6P)pathway,themajorroutefortargetinglysosomalenzymestolysosomes.

PrecursorsoflysosomalenzymesmigratefromtherERtothecis-Golgiwheremannoseresiduesarephosphorylated.IntheTGN,thephosphorylatedenzymesbindtoM6Preceptors,whichdirecttheenzymesintovesiclescoatedwiththeclathrin.Theclathrinlatticesurroundingthesevesiclesisrapidlydepolymerizedtoitssubunits,andtheuncoatedtransportvesiclesfusewithlateendosomes.Withinthislow-pHcompartment,thephosphorylatedenzymesdissociatefromtheM6Preceptorsandthenaredephosphorylated.ThereceptorsrecyclebacktotheGolgi,andtheenzymesareincorporatedintoadifferenttransportvesiclethatbudsfromthelateendosomeandsoonfuseswithalysosome.ThesortingoflysosomalenzymesfromsecretoryproteinsthusoccursintheTGN,andthesetwoclassesofproteinsareincorporatedintodifferentvesicles,whichtakedifferentroutesaftertheybudfromtheGolgi.[G.Griffithsetal.,Cell

52:329;S.Kornfeld,Annu.Rev.Biochem.

61:307;andG.GriffithsandJ.Gruenberg,TrendsCellBiol.

1:5]Figure6-40.Themannose6-pho135.ProteinSorting

Overviewofsortingofnuclear-encodedproteinsineukaryoticcellsProteinsareimportedintoorganellesbythreemechanisms:GatedTransport:TransportthroughnuclearporesTransmembranetransport:ER,Mit,Chl,PerVesiculartransport:ER-Golgi-PM-Lys,Endosome5.ProteinSortingOverviewof14

Roadmapofproteinsorting

Roadmapofproteinsorting15Proteinsorting:Proteinmoleculesmovefromthecytosoltotheirtargetorganellesorcellsurfacedirectedbythesortingsignalsintheproteins.Proteinsorting:Proteinmolec16SignalpeptidesandSignalpatchesFigure

6-8

Twowaysthatasortingsignalcanbebuiltintoaprotein.

(A)Thesignalresidesinasinglediscretestretchofaminoacidsequence,calledasignalpeptide,thatisexposedinthefoldedprotein.Signalpeptidesoftenoccurattheendofthepolypeptidechain,buttheycanalsobelocatedelsewhere.(B)Asignalpatchcanbeformedbythejuxtapositionofaminoacidsfromregionsthatarephysicallyseparatedbeforetheproteinfolds;alternatively,separatepatchesonthesurfaceofthefoldedproteinthatarespacedafixeddistanceapartcouldformthesignal.SignalpeptidesandSignalpat17Gatedtransport:

Throughgatedpores—Nuclearpores;Nuclearlocalizationsignal(NLS);Foldedandassemblyformtotransport.TransmembranetransportERsignalsequence,Mit,Chl,Per:Leadersequence;Throughtranslocononthemembrane;SingleandUnfoldform;HelpedbymolecularchaperonsGatedtransport:Throughgated18VesiculartransportBudding,transporting,dockingandatlastfusionwithtargetmembrane;Assemblycoatedproteinsonthevesicles(Clathrin,COPIIandCOPI);OnlyProperlyfoldedandassembledproteins;Theorientationoftransportedproteinsandlipidsisnotchangedduringtransporting.VesiculartransportBudding,tr19最新考研资料：细胞生物学六章基质与内膜(中)课件20考研资料：北京大学细胞生物学第六章基质与内膜(中)考研资料：北京大学细胞生物学第六章基质与内膜(中)4.ThestructureandfunctionsofLysosomesA.CharacteristicsofLysosomes①Lysosomeisaheterogenousorganelle:PrimarylysosomesSecondlysosomesheterophagicautophagicResidualbodyPrimaryLys.SecondLys4.Thestructureandfunctions22最新考研资料：细胞生物学六章基质与内膜(中)课件23最新考研资料：细胞生物学六章基质与内膜(中)课件24最新考研资料：细胞生物学六章基质与内膜(中)课件25最新考研资料：细胞生物学六章基质与内膜(中)课件26最新考研资料：细胞生物学六章基质与内膜(中)课件27最新考研资料：细胞生物学六章基质与内膜(中)课件28表1.神经鞘脂贮积病疾病缺失酶类主要贮积底物后果GM1神经节苷脂贮积症GM1-半乳糖苷酶神经节苷脂GM1智力迟钝，肝脏肥大，骨骼受累，2岁前死亡泰－萨二氏病己糖胺酶A神经节苷脂GM2智力迟钝，失明，3岁前死亡法布莱氏病-半乳糖苷酶A三己糖神经酰胺皮疹，肾功能丧失，下肢疼痛山霍夫氏病己糖胺酶A和B神经节苷脂GM2和红细胞糖苷酯与泰－萨氏疾病症状相似，但发展更快高歇氏病葡糖脑苷酯酶葡糖脑苷脂肝脏和脾脏肿大，长骨腐蚀，只在婴儿期发生智力迟钝尼-皮二氏病鞘磷脂水解酶鞘磷脂肝脏和脾脏肿大，智力迟钝Farber’s脂肪肉芽肿病神经酰胺水解酶神经酰胺疼痛性与退行性的关节变形，皮肤瘤，几年内死亡Krabbe’s病半乳糖脑苷酯酶半乳糖脑苷脂髓磷脂缺失，智力迟钝，2岁前死亡脑硫脂沉积芳基硫酸酯酶脑硫脂智力迟钝，前十年死亡表1.神经鞘脂贮积病疾病缺失酶类主要贮积底物后果GM1神经29D.BiogenesisofLysosomesFigure

6-23

Thetransportofnewlysynthesizedlysosomalhydrolasestolysosomes.

Theprecursorsoflysosomalhydrolasesarecovalentlymodifiedbytheadditionofmannose6-phosphateintheCGN.TheythenbecomesegregatedfromallothertypesofproteinsintheTGNbecauseaspecificclassoftransportvesiclesbuddingfromtheTGNconcentratesmannose6-phosphate-specificreceptors,whichbindthemodifiedlysosomalhydrolases.Thesevesiclessubsequentlyfusewithlateendosomes.AtthelowpHofthelateendosomethehydrolasesdissociatefromthereceptors,whicharerecycledtotheGolgiapparatusforfurtherroundsoftransport.Inlateendosomesthephosphateisremovedfromthemannoseonthehydrolases,furtherensuringthatthehydrolasesdonotreturntotheGolgiapparatuswiththereceptor.D.BiogenesisofLysosomesFig30Mannose6-phosphateresiduestargetproteinstolysosomesTargetingofsolublelysosomalenzymestoendosomesandlysosomesbyM-6-PtagMannose6-phosphateresiduest31PhosphorylationofmannoseresiduesonlysosomalenzymescatalyzedbytwoenzymesRecognitionsitebindstoSignalpatchGlcNAcphosphotransferasephosphodiesterasePhosphorylationofmannose32Figure6-40.Themannose6-phosphate(M6P)pathway,themajorroutefortargetinglysosomalenzymestolysosomes.

PrecursorsoflysosomalenzymesmigratefromtherERtothecis-Golgiwheremannoseresiduesarephosphorylated.IntheTGN,thephosphorylatedenzymesbindtoM6Preceptors,whichdirecttheenzymesintovesiclescoatedwiththeclathrin.Theclathrinlatticesurroundingthesevesiclesisrapidlydepolymerizedtoitssubunits,andtheuncoatedtransportvesiclesfusewithlateendosomes.Withinthislow-pHcompartment,thephosphorylatedenzymesdissociatefromtheM6Preceptorsandthenaredephosphorylated.ThereceptorsrecyclebacktotheGolgi,andtheenzymesareincorporatedintoadifferenttransportvesiclethatbudsfromthelateendosomeandsoonfuseswithalysosome.ThesortingoflysosomalenzymesfromsecretoryproteinsthusoccursintheTGN,andthesetwoclassesofproteinsareincorporatedintodifferentvesicles,whichtakedifferentroutesaftertheybudfromtheGolgi.[G.Griffithsetal.,Cell

52:329;S.Kornfeld,Annu.Rev.Biochem.

61:307;andG.GriffithsandJ.Gruenberg,TrendsCellBiol.

1:5]Figure6-40.Themannose6-pho335.ProteinSorting

Overviewofsortingofnuclear-encodedproteinsineukaryoticcellsProteinsareimportedintoorganellesbythreemechanisms:GatedTransport:TransportthroughnuclearporesTransmembranetransport:ER,Mit,Chl,PerVesiculartransport:ER-Golgi-PM-Lys,Endosome5.ProteinSortingOverviewof34

Roadmapofproteinsorting

Roadmapofproteinsorting35Proteinsorting:Proteinmoleculesmovefromthecytosoltotheirtargetorganellesorcellsurfacedirectedbythesortingsignalsintheproteins.Proteinsorting:Proteinmolec36SignalpeptidesandSignalpatchesFigure

6-8

Twowaysthatasortingsignalcanbebuiltintoaprotein.

(A)Thesignalresidesinasinglediscretestretchofaminoacidsequence,calledasignalpeptide,thatisexposedinthefoldedprotein.Signalpeptidesoftenoccura