oS b- pe ee | C Ch Uy: Vesicular Flux endorgtoss Fevurtesis Fe geemeeete oes cee = PM assisted. transports 1 | -Movemenk of molecules in L out of cells — Fequires energy 2 vesicles =used by cells to transport lage macromolecules - Atypes cf transport endocytosis Cxorytosis vesitle Formesibn yest Fusion, ’ Coudding or with PM ) Fission)” From the PM A~ Endocytosis. —cells fakes in substines by vesidle. Formation Cludding )) =f portion sf PM invaginates to Con contribule Fo: \ envelope a substance = the uptake of nutrients | @ | - Cegulation of Signaling / then the vesitle gets dekached. Molecules ) Contras co osmotit { — PM arta \y with ves@le detachment pressure, — fundion of syrapses types SF endocytosis + — ——— = Phagocytosis (uncoated, forming Pseudopeds) ae Pinouytosis Cancoated) 3. Receptor. mesiiaked endocytosis Catathrin RadapKin Cooked prt ) [ 4 potocy tosis Ccoveoloe) @ 4(ts Phagecybesis. — For partitles (solid. Sobstanes) ———~—_ ~ cell engulfs Parties into vesides via Pseudopodia 4 Formation Govoliing corked actin Network ) —> Phagowytosis Forms large vesicles (vacusles of Phagosomes ) thon vesicles “YD Formed. by other dypes of 7 endocybesis 7 somes Fuse with lysosomes pI 'y «iN Pprototea , Phagocytosis tS a Farm OF feeding = In mnalkcellular organisms Phagocytosis 7 “importank For purposes cthem then nutrition — corried ouk by spedalized cells Professional Phagowres” 5 in Mammals Wree classes of WBLS ad as 7 Professions) phogocytes 4 =, Geshepi) (denarthe eel s | Play a pole } (in Scavenging ) | anne ad y these cells all QB cells Hot evelop From hemepoiet2 hove died by ston cells , B they defend apoptosis US against infecKon by @ ingesting invading prerDoryanrsinsbe Phagesomes have chamebers that art determined by the size of ‘ingested parkicle = Phagesomes Fuse sith lysosomes inside fhe cell, | then ‘ingested Material 7S clegmded —> indigestible substances ual remain In the lysosomes Reercing Cesidus) badies — TO be phagocytosed ; parkiles musk bind to Susfice Peceptos L Phage cybosis TW a Hriggered Process ConiKe Pinocykosis ushich 7 consHikudive 2 occurs continuously) a | ¢ We best characterized triggers are anbibudies bind Fo infectious Mi Cro OBaniS M5 to Form o cook L in whith the Foal region oP each antibody CFe region 7 exprsed an he exterior , binding “dnduces Phagorgere cell | Fo extend pseudapeds Hod engulP rhe arkile £ Fuse ot Fee tips to Form aw phagosome G3) Hh ankbady cot 7s recogiited by speahr Fe receptors on sufface of (Macro phoges p neateophis[Other classes oF receptors that promote Phagouytosis? | be recagnite complement components (collaborake sith | antibodies in Horgehiny mire bes) | | Aarecagnite directly “oligosaccharides on surface of | NTO 0 PANES | Ni distribusie. | Be recagnee opephi2 cells op, lose assymebic skribudion | BF phospholipids in PM Qudy caged is now “s exposed on oubside He cell b brigges Phagocytosis oF the dead cll 2-Pinowjtesis: fer Fluids 2 dissolved solostones > ~~ _ = Deonspeafic endocytosis | ~Moleades are +fansporked to the | | Cell by unceaded vesitles — Ne Formation oP pseudopods (3 Receptor medrared endawitasc: _ Farms coated —— vesides asith inti aan clathrin-coated pits provides Selective (clathrin 2 adaptin concentrating Mechonisne coak ) et A-OCS IN o defined locdion on PH Fitiensy of thet hes speafz receptos Uwheratieaon oF hypads Qo coated pit ) — —allows transport SF speciFiz Molecules that hove spedfre >) recepkors | ~No Formation of Pseudopods | @ is~ Macromolecules bind to Complementary transmembrane cecepror proteins accumulated 7 Coated pits t enter the cell as recepkor_ mac maleale complexes in Clathrin- coated vesidles Ex; LDL receptor mediaked endocytosis : iF uptake of cholester) 75 blocked + cholesters! accumulates in blood contributes to the formdion Hin blood vesse) walls f atherosclermbe Plaques, depesits sf bpid 2fibrus issue | b Con cause strokes Q heark attaks by blodkiag blood Flow Cholesterol is transported in blood as cholestery) esters in the farm SF LDL Cow density Lipoproteins)ered _noiest Gore TS a single —pass Hansmenbrve = — ghycoprtan 7. oa pp ee LOL receptor’ = oor x een Shas LDL recephors. diffuse until J They assocate wsithy ain Woked | uv pits "at we membrane bend s ) QL invoginakes \ ) LOL bound to LDL recephos in the coated piks ore rapidly —_—_—_——————— Tnternalited ‘in cooked vesiules | =) | _ He vesitle Uncoaks | 2 k a After shedding thar clathrin | Ja Goats the vesiles deliver 7 rs uy their contents to early | endo somes ) | aoe \ oO Near Reger the eel periphery)| | | | Phen ik Fuses sth the endosome | | | | | i | | —the endoseme hes Low pH WS causes the LDL receptor to release LOL AL ADLis delivered vin loke endosomes to lysosomes.| recephoss byrje0 byHose tefea (returned to PM) e' |¥— ate & ee | @® | J > \ a PPP PP into cyt esol to be \ used i the sypthesis \ (=) BF new membroves. | — —_ LDL Porkicies (e° 2)) Need ta be assembled Sye ve 1 \ Free cholestee) is bested itene contents | eae delivered $3 a o G 2 lps 1 9 0 Ysosomss — : | | \ ED. a “hydlelghit entynes (rgest the parkittes) cholesteryl lL esters in LOL EE hydmlysed ee to Free cholesterh @-iF too much chelestes) accumulobes in a cell =p Phe cell shuts off both its oun cholesterl Sypthesi® AL syplhes’s SF LOL receptes prteas =p it ceases either to make oF to take up cholestenl- @ 2 Ggond binds to membrone receptor i) receptor — ligand migrates to clathrin-coated. pik L © endocytosis L @ vesde loses clathrin coak ; { © ceceprors 2 Migoads Seperake L © Lgaads ge to lysesemes of Golgi For precessing @ transport vesitler with receptors Moves +o Me cell Membrane. L | @® tronspork vesicle 2 cell membrane | Fuse Cmembrne recydling ). |Example 2) “WansPerrin. detivers iron wshen apo’ Fetumed to Moved. +o o the Same PM # domain of | domain From eM | rransferrin returns 3. Pathoys are possible fr transmembrane receptor | Proteins thet hove been @ endocytosed: [oakeeh Bey came endocytosis to the neutal pH sf Ecr, ab disseaotes from receptor & therefore 3 Fee to pick up | Mere iron 2 7 cyde ager. begin Fecepror— apotransferrin Aubulor extensTons oF early endosome QL From there % recyded back to PM 2 FransugFosis Complex enters the ee oe) eecephoe ge to lysosomes to be degraded me \ | by receptor -mediated + Transferrin: Soluble protein , carries iron in blvod = Cell-surface transferrin receptors + deliver Fransferrin with 7S bound Won to early endosomes by receptor — mediated ay: endo egtests, the Lous PH in endosome causes transPerrin to release is bound won | Bub the iron - ] Free trans Ferrin itself (oPotransFerril ) Pemaans bound to its recephor| | =p transferrin receptor Fellows the recycling Pathusasy bout alse iF recydes Fs Jagond | Crronsferrin shutHles bode £ forth bho ECF A endosomal compartment => aveiding lysosomes ) | Grample3) EGF receptor 1s degded i lysosomes: | I (EG FLTS Small, extraceituler sign) protein | _sHimulates efidermel 2 various other calls to divide | + unlike LDL receptors, EGF receptors accumulake iN | clathrin-coaded pits only oFter binding EGF as most of EGF cecephors de nct recydle jour ort elegracied in lysesemes lise with Phe ingested EGF. |. EGF binding ——» First octivetes intracellulor Sigrbing Pothuseys then Jeads to a Sy in EGF receptors on cell Surface é “receptor down—requiotion” proces (reduces cell's Sensitivity to EGF)_ Example) Moternal antibsaies can be transferred acres epi vol cell Sheets by ‘Transeykosis: ONE OE RO a a | t= lumen F gut 73 acide Ak WS low pH, | antibodies in the tril bind Fo spedFit. recephos on apical surface of gut epithelral cells , l } Fecephor—ontibody Complexes are iadcme- finternalited via Cothrin-cooded pits ? Avesicies | AL delivered to cantly endosomes | | | Complexes remain Spkack 2 are retrieved iin Hreasport vesides thet bud From eorly endosome | | On exposure to} & subsequently fase neutral pH of ECF, | Uaith base leterad > antibodies dissoate ) | domain 6 PM from Ceceptors Q ) eventually enter the. | (B® Newbern's bloodstreamos pony |H_ Poto cytosisy — Formotion of Cavenlae (A = occurs in defined location on PM | —— | | has specifi. receptors | o.ceumalating the roFts | ridh in cholesterl | glycosphinge lipids | @ GPL - anchored | membrane Potans eee = Coveolae contain coveolin integra) protein 27s a hoirpin protein multipass integral wN- 2 C- Ferminals membrane. protein constitube a permanenh - Dekeregeneous cover sh cytosol . # Sikes of surface. of Iipid moFEs, | palmitoylation £ conestoe 2 of cena phosphorylation endousto He vestoules: Baan | .caveolin oligomers produced by caveolac. Concolin ligomess Form Conenlae assembly debachmenk form coveoloe daiter her contents cither te | | endosome1sKe 9f PH on the opposite Compartments side of polorized cell | Ta SY) | @® ‘ process= Someviruses ener Phe cell in vesidles derived From Caveolos oY db = | 4 viruses First delivered to endosome whe compartment then move to ER Gahere they eddrade . | Hhar genome into cytese! to Stork their infecdibus cyde iS + pokocytosis twas based on receptor mestabed uptake | G_methyterahydrafoloke Covecloe con nkerralize Small malecules,vons, 2 moleases Ike cholera tox) s(by binding +o a GM1)os well os macramolectlr complexes Ile vinus. a endothe cells use cavestae fo transport Hyfosin Fo 4Boue space (Transcytosiz; 1- Plasma proteins are | concentiaded in Coveclae 5 D Form vesrles | vesizles cross the cell sikh Pre help From cyte skeleton | L hen undergo endoryFos3 | yesile conents ore. released jnto ntesitral 3} Fluaa by exouytosiz 4)| | ") B- Exocytosis! requires energy & or of 0 ves@le wath PM to eject speaFiz secretion Fusion Prducss LPM aren 7 vesiles are Mainly produced by Reguloded secrekory Pathoy Golgi L conshitutive secietoy Pathscoy yesizles destined For PM 2 « Soluble Proteins Qother ally stored lore | 1, transpor leave s Golgi Nekwork substances are wiki an Seerekory vesiles far release (hembra B protems 2 unpals tn these vesicles provide hew companents Fer PM ths Polhoay 7s Found pointy 79 cells Thad secrete hormones, or Agestive uohile peuorransmrrers y Soluble proteins jaside the enzymes veszles are secreted to racellulor space ext a «Pasion of vesidles with eM 7S colled exocytosis Spin mis way y Cells produce Q secreke Most oF mareah yeni L glycoproters of €dM 5 f Ns)AieSides with a AV dessita) Cyteseliz Cook (visuslied Mee theses cara - cor av I vesides |. COPT vesides « Clethrin vesides To invelve. 3 pringpal elements: wo transmembrane. proteins / kyroselie Proteins sf dener compartment ae ehave pephide sequence ab cytosol side Mot 7S able to promote Polymerization of cooding these membrane proteins Gn be: 1) thed will polymerite 2 © fo Ferm the coating cop'< Freasmembrne) carrier $eca3/secay Formed | proteins complex , Ft 7 porens | b | seei3/sec3s || CoP a frensper: \ complex, Sobunits, Soluble ease, 1) \prekein Secle/ | by EM) Rares er angered _as=nonweded- r pad fasiltate ‘sHimalade, exchenge F || GTPase GOP +0 GTP || activity of ongenf oN caveolin vesile Ccaveolac) | (difficult to visualite $ | dé ) Honemeric. G Ppeteins, \ Weir Pegulako ny ( Fxetors,.2 GTP ockivity 15 Controlled. by Facto thet inFlucnce their ably te bind 2 hydlyze GTP to GDP:© Monomeric G proterns are post of A types of Coakomes os ec ini Sart p ot ARF ossodated Fasnity asso dated with Cop osith COPT A = Monomei2 G proteins activate adaptin Q indiresiy contribute te the constitudian of clathean Coading usithout being a park of it. + Clothrin coated vesiles 5 mediate transpork From Goigr 2 From PM ae 4 COPE b. COP T csadedk vestlec —> Medizde transport From ER 2 Ga gf_CBkernac Bssomted GTPase + COPIL _, transport For ER to B-Golg 2 Sarpy Gane grade) — + ARF Cetrogade ) «Clothrin Radkpkn _,5 fam Go gi +o. endasome Ay | from PH +o endosomes. ie RF GTPas os | ( SoperFest) scop I — From B-Gol§ to ERFormation of COPE. vesicle: a ———— Sor] 7S a mea myristoylated G protem when attached to GDP, ‘ks hydrophobre tail Cnyriskoy) grP) TS trapped in the proban 4 Sart is in Soluble 2 Form in the cytesel Cinactive, soluble Sart GOP) A speafr GEF (ER membrane protein qlled Secla ) binds to a | dgre solic Ser! GDP | GEF replaces GDP of | Sarl by GTP. 4 3 Sori. GTP releases its hydrophobic teal enabling at 40 be anchored in ER membrane sig) = Sorl-GTP recnits COPI subunits to the | Menmbranc, | @}= Sort membrane binding , ETP exchange | a- COPE assembl Seorl binds seca3 /secay, then assocadion usith cargo ron then bindiry of seci3 /5ec3 | then GTP hydrolysis i then Coot disassembly Cuncoored vesizle) + UNtwakings One vesidle 7 detached 7 : One St Phe coat Proteins Play the role of GAP \ Q stimulokes the GTPase activity of Sart l Sort_ GDP pulls out Ths hydrophebit, tail Fegoins the cytoplasm hus, AtSperging Phe ) Conshitucnts of Whe cook.+ Formation af COPT vesile: —————___!__:_= ~ COPT cock consmts of a hepkamer® protein Complex —stenned Cootomer QR the small GTPase ARFI 4 Formation SF clathrin 2 adapkn vesicles: ———SSSSSSSSSSSsSSSSS | ~Fequires interaction OF if, cargo recepkor Jo clap hin 2 Coak protean (COP of | clathrin ) | # dynarnin Galvin | ~clolhrin risReletatr triskelion 7s composed SF B heovy choirs 2 3 Light choing | adapkin \ (| - # types sf adaptation pratans =p 7 cliversity of papas cykosait. Coadks 7 oR dalvin Q odeptin 1 | vesicles [seach type 7s specific Far o grp st carrier . sels casge protdas |— activated by monomeric G proteins of ARF Fanaty Which are specifre bo them Budding oF cloltein vesidle: 7S o transmembrane protein | ob pidked up by Care receptor cohith TS a transmembrane Protern > bind site 7 on lumen side @) ee eR Prea Clotbrin 2 adaptin coodity » Tens- Golg membrane the Cytosolit, SurFoce oft a PM this net deforms 2 | Forms hexagons) and Pentagona) meshes cohich ee Causes the budding of the vesidle covered with dothrin 4 3: Aypep. chains g Se peas { rogh | each clathrin consists of - 3 small polypep. chains es exe a oe assemble $9. 0 bosket he convex of hexagons oa pentagoas +o form Coated pits On vyfoselit Surface oF membranes .« Adaptin: —multsobunt Complex a) —W clobhrin-cooted vesicles —Pequirel tox. bind clathrin cook +p Membrane 7 + tp various trensmembrone Prokeins Gndudig Corge recephors ) (Cook assem * sat 3 oSsembly P aS Gaye Selection , he bud (veside) jushizh Hien pinches fF. = GTP _driven press + detachment: dynamin constrizhs the neck of NCO odTAg: coot prreins are released before. 4 being transported ay the cytesal | under the acten oF constitubive, ATP_dependent HSP Fo —p Clothin Dodaplin protens are recycled 9 | in the cytesol » products incorperated after Fixation to a receptor; Hormones —Groth focros 7 — toxins virus > —plosma transpsrk proteins —Tomuns gt bins @®=D Mest transport vesitles —s Form From Specialized, Coated Pegions of membranes bud sfF as costed vesitles se by a cage of eo Proteins (on cytoselit surface) i | | | | | | before Sing ust | Farge membrane, the | Cpecdis discarded allows The 2 cytosoliz, Membrane surfaces to iMteract directly £ Fuse | —t COat has 2 pringpal Functions: : pt 7 = @ Tr cdncent: ® Assembly SP Coat Sp Membrane. Proteins ‘nko bashetlihe. Proteins an a \ lattes dlefarms the Specialized membrane Membrane patch es es = , pol a give. Be fo yesitle Molds the. Forwing | Membrane vesTdes / ma ane oe Tt helps select the] appropriate molecules For transpork i vesizles asith Sastie, | type st coat fas | hee uniform size || \ eVESiUle tare sn cells; | ] | endocytosis path | usa y | s p “J + Membrane Patt endesome L Lode endosome U lysosomes - Secretion po: 4 : cone theses » ER 995 — MeMbane, gay gelgi — seerebory vesicles —» membrane gelgi —s late endosome—slysesome p backusora See pothoas: Gelg ER late endosomes gelg easly endosome _» Membrane @ Prokeins vith mannose 6 - phosphate (MSP) marker Jer diverted +o Jusesomes (via late endosomes) Gn CloShrin—coaked transport vesicles 4 | soo J} G@) Protens usith signels directing them to secretony vesicles g \ yg [er Concenkroted an. Such vesitles as pork GF regutoted Secretory pothwoy Chet 18 present only in Specalized. secretory cells ) | @ to unpolorized Gls , proteins with no spedal Rabkures \ | si delivered ko We coll Surface by cons Htukive swurte sthusay (de Faulk pothus id) eS pees oy)- Mannose 6—P pethosay | y synthesis of lysosome) enzymes in ER i | rransprtes ts cis — Golgi | where it is ging to be phosphorylated =D Mannose— 6 — phosphate transported to > trans Golgi L Coshich contains H&P receptor) Tnkeraion bho Mé6P_2MEP recephor H6P receptors become concentrated L budding of Ihe vesicle Clothin— coated vesicle) whith contoans recepkors bound te lysesemal enzymes Vacoating of the vesigbe L uncoated Hranspark vesizle, will Fuse sith Lede endosome Clow pH ) seperation of ena From s | receptors 2 also os or enaymes ee Pia recytling of COs ap ieeees MEP recepkors¢ Exocytosis sf secrebory vesiles: —_—_— © Secretory Pereins are Pachaged iN trans. Gotgy | by Selective aggregation of these proteins netusrk (TED) @ Secretory vesitles Hak Jeaue TEN | Form “immature, secretory vesicles thes are loosely wrapped oreund Secretory proteins @ As tre vesicties Mature Meir Contenks become. concentrated as the result of: _ oy B membrane Progressive acdlificadran Preteans become concentrated (are vate amen os they move From ER +e ecu Mat results From bet ot extensive. rebre grade progressive retrieve) process mediaded by COPT _cooted vesides thet exclude them > also Teough Pecy ding oF clathrin — doored buds on surface of mioture Secretory vesitles ie the Golgi concentrasion of ATPL driven HT pumps in the vase vesicle membrane ¥| ae | bei ® proteins ore robes luteal He P ed Synhesied as 7) | Processed during Formation )—p hosmonrcs | of Secretory vesteles eee | Cinochive ) | © Secretory vesides sci near Proteolyss | PM unk! srqnal Cpr ymotiz. | until signeled to releose levee ) | Weir contents ic tive. Molecule © hen secretary vesicles / 5] Fuse usith pM | L > | Whar Contents are. lis Frem the cell by exocytosis QR ther membranes became Part of PM 4 3 steps are involved in Synaptic Newebransmib ters ] \ Sor be sis ¢ = ee Be tNesidle braF Fic vesicles Hak Frenspork Probeins From golgi will use motor proteins A Cytoskeleral track to get closer Fo the tagek |A- vesi@e peter “involved in. ConcenFrading SynepHe vesicles ab the Sytapse. | (B- vesitle deck Secretory vesitles Fransiently dock | at PM ap leading te priming 2 estoblishment oF conknuity bus Yhe, Spacing Blayess.Hevesicle Patvith all Molecsler rearrangements 2 ATP dependent probein 4 Lipid modifreations take place afer initia) docking of Sypeplic vesidle. buk before exouybosis S—vesicle Fusion: Honastent yesitle Fusion 7 driven by SNARE prsteins =P resulling in celease OF vesicle contents into extracelluler space SyMephe vesicles containing newotransmibkers clock sith PM L the docked vesiles ore primed for secretion IN of ATP /Mg>+ dependent Process Heat readies them For immediate Pelease 1 response toilsal Zin GP Sécondory Fo membrane dePolartzodion | Nese 2PM Fuse Qvesvle conkenks are released into Cxhracelular spore“We oriented transport of veszies: Ee ————————_—_— +Hode of transport: Shea LO | Ss Shork distances, Over tonger distances, vesicles Move by vesitles move ako, cliF fusion Frads of miuatubules Lore moved by motor prstdins, Kinesins yor etyncins —ergerng —7 inves Se oa ee Ctesclit aK which) Fachkade interachions bho eben (hee = —are complex ahs —Sesve oS ackess lobels For vesidie tra FFicking poleFining he identity Q routing of vesides —ore G-proteins Shores ‘Shares (esnares) Ck-snores) jncorported — ip corporated pin plex Farnily into vesicle inko fe — docking by TnkeSOGiON deo membrane, # V-Shore 2 E- snore Proteins, ay spearie proteins = Shares eccure OS Complementary pars sf prkdns @3) membrane.GTP_ Binding Rolo Prorens as Reguloders of vesitulos— Frgfi2y Ras probes bind 2 hydrolyze GTP Ye cycle sf GTP binding ot 4+— hydrolysis regulates the rade a af vesicle fasion Rake of. i vesicle Fasion ee i) GOT (cgbesole protein) Catalyzes eee The exchaige oF bound GDP for GTP Rab- GTP i Inducing & conformadbnad in Rob Het enables it to bind to a surfece Preketn on o Portrculor henspork vesitle After vesicle Fusion, GTP bound +s Reb prstein iS hydrolyzed to GDP e release of Rab protein+ dedkisg by SNARES: ® Pe | |-Assembly of SNARE complex: = ossembly oF 8 } HH _ J helices? é ft vVANP. Cv-Shore | > reduce Free energy required | Yo juxtapose, membranes 2 + Syptasdine (e-store ) | accomplish vesitle- membrane Fusion ~ A SNAP_ 25 (E-Store) | | — Disassembly of SWARE complexi by NSF 2 SNAP | requires ATP B yeside rintraccular Adeckiay SF membranes Paquire cnegy + Fusion sith a» membranes require Cat | 1 Fusion invelves a consered set of protems Heb: @ A Mediates targeting of vesicles +o appraprrake Fusion porkner b. riggers the Fusion process itself he Oo ieolke ie epelymerization oF ff the qesicls coat proteins J ee e/ uncevers: V-SNARE Ginkeg “ih ” oe / foe ¥ oe Per - ce i / ees intorperaded. into a Hransperk veside os i lads From the donor is argonelle The membrane oF each type of forge membrane in a ce conkamns the Pustaen © Pproten SNAPS 2 one of Mere inkesral proteins CE SNARES) the| spectre V-SNARE on each type of transpork vesicle. tongets the vesidde to Tks correct membrane Faston Parkner