A Journey Through the Exocytic Pathway Sophie Béraud-Dufour, William Balch

A journey through the exocytic pathway Sophie Béraud-Dufour, William Balch

To cite this version:

Sophie Béraud-Dufour, William Balch. A journey through the exocytic pathway. Journal of Cell Science, Company of Biologists, 2002, 115 (Pt 9), pp.1779-1780. hal-02266871

HAL Id: hal-02266871 https://hal.archives-ouvertes.fr/hal-02266871 Submitted on 16 Aug 2019

HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Cell Science at a Glance 1779 A journey through the respective transport steps and/or exchange factor (GEF) Sec12, which compartments. In both the upper and results in the formation of a microtubule- exocytic pathway lower panels, the mammalian proteins dependent scaffold that initiates cargo Sophie Béraud-Dufour and are labeled in black and yeast proteins selection through tubular intermediates William Balch* are labeled in blue. If the mammalian (referred to as transitional elements). and yeast proteins utilize the same Department of Cell Biology, The Scripps Research Coat assembly and ﬁssion is completed Institute, 10550 North Torrey Pines Road, La Jolla, nomenclature, they are highlighted in by the recruitment of the Sec23/24 CA 92037, USA green. The numbers within the red guanine nucleotide activating protein *Author for correspondence circles refer to additional effectors (e-mail: [email protected]) (GAP) complex and its regulator, the (shown in the lower half of each panel) Sec13/31 complex. Upon ﬁssion from that participate in the indicated transport Journal of Cell Science 115, 1779-1780 (2002) the ER, COPII-coated tubules/vesicles © The Company of Biologists Ltd step. lose their coat in response to hydrolysis of GTP. They are subsequently believed The poster is composed of three panels, All eukaryotic cells contain numerous to fuse to form the intermediate which represent the three major protein membrane-bound compartments with families required for the journey of specialized functions and therefore compartment (IC). Here, proteins cargo through the exocytic pathway. unique protein compositions. The exported from the ER can undergo two These families are the ARF and Sar1 journey of proteins between these different fates, either escaped ER family GTPases, which are involved in compartments starts by co-translational resident proteins and misfolded proteins vesicle formation (left panel), Rab insertion into the endoplasmic reticulum are transported back to the ER via COPI- family GTPases, which are involved in (ER). Exit from the ER is mediated by coated vesicles (left panel), or normal vesicle targeting (middle panel) and COPII vesicles from 100-200 export cargo destined for downstream SNARE family proteins, which sites distributed throughout the cell (left compartments is retained in IC elements participate in vesicle fusion (right panel). panel). COPII coat assembly is regulated that are transported to the pericentriolar The upper half of each panel illustrates by activation of the Sar1 GTPase by region, along microtubule tracks, where the localization of these proteins to their the ER-associated guanine nucleotide they fuse with other IC elements to form

Regulated pathway Constitutive pathway

Regulated pathway Constitutive pathway Regulated pathway Constitutive pathway Syn1,2,3,4 (

Rab8 Syn1y 8 Rab3a 11 8 Syn1a,b Syn2S2y Rab11 Syn3S3y 9 Rab3b,c,d Rab17 7 Syn3 9 Rab26 Syn4S4

Sec4p Sso1p,2p

(Secretory (Melanosome) (Melanosome) (Melanosome) granule) (Synaptic (Secretory (Synaptic (Secretory (Synaptic vesicle) granule) vesicle) granule) vesicle) ) 4 Syn7, Syn8 5 AP3 AP1 14 10 Rab27 6 3 4 Arf1 Endosome Rab6a Endosome Endosome GGAsG (Ypt6p) 4 AP4 Rab5 Rab9RRb9 Tlg1p,2p AP1 (Ypt51pY ) Rab11 Rab6 Syn11 4 5 Rab15 Rab8 Syn13 5 Syn6 (Tlg1p) 5 AP3A Arf1 Rab9 Rab10 7 Syn10 (Tlg1p) Rab7 TGN Rab11 Syn7 (Pep12) Clathrin ClathrinC (Ypt31p,32p) Syn8 Syn11 Rab12RRb12 TGN Syn16 (Tlg2p) TGN Rab17 Late endosome Late endosome Late endosome (prevacuole) (prevacuole) (prevacuole) Rab6 Trans-Golgi Trans-Golgi Rab10 Trans-Golgi Rab1(Ypt1p) 5 Rab7(Ypt7pY ) Medial-Golgi Rab6 Rab6Rb6 6 Medial-Golgi 2 Rab24 Medial-Golgi 3 ? Rab12 Syn7 Syn5 Rab33b 13 (Sed5p) Arf1 Cis-Golgi Vam3p Syn8 COPI Rab1((Ypt1p) Cis-Golgi ? Cis-Golgi Rab30Rb30 ? 2 Arf1 Lysosome ? Rab33b 13 Lysosome Lysosome COPI (vacuole) (vacuole) (vacuole) CGN Rab6 CGN 2 CGN Rab24 ? 2 2 2 Arf1 COPIC 3 Syn5 IC Rab1(Ypt1p) IC IC Rab2Rb2 15 (Sed5p) Arf1 COPI Syn5 2 12 Rab2 1 Rab1 (Ypt1pY ) 1 Arf and Sar1 1 (Sed5p) proteins 10 Sed5p Sar1 SNARE Bos1p COPI COPII COPII Rab proteins proteins ER ER GGAs ER Ufe1p Clathrin Syn17 Nucleus Nucleus Nucleus Smooth ER SNARE components and partners involved at indicated steps Proteins implicated at indicated transport steps Proteins implicated at indicated transport steps 1 Syntaxin 5 (Sed5p) 6 Vacuole homotypic fusion in yeast 1 Rab1a,1b (Ypt1p) 3 Assembly of GGA-containing coats at the TGN: 4 Rab9 10 Rab27 [myosin receptor?] * BET1 (Bet1p) Isolated 1 COPII coat complex. Many additional RabGDI (Gdi1p) [RabGDP-state chaperone] p40 [fusion activator] Myosin Va [actin motor] Primed the GGA proteins are recruited by Arf1–GTP Mss4 (Dss4p) [empty-state chaperone] Melanophilin [Rab27 effector] SEC22b (Sec22p) vacuoles vacuoles components are required for export Tip47 [Rab9 effector, Membrin (Bos1p) LMA1 Sec 17 LMA1 and in turn recruit cargo proteins (MPR), clathrin p115 (Uso1p) [GM130, giantin binding protein] Vam7 ATP ADP + Pi * MPR-interacting protein] Sec 18 Vam2/6 Ypt7 Vam7 of specific cargo. PRA-1 [Rab receptor ?] Ypt7 and accessory proteins (γ synergin). Rab7 s-SNARE Vam2/6 TRAPP (TRAPP) [GEF] v-SNARE: F-Actin Nyv1p t-SNARE: Sec31 Gyp1p [GAP] 2 Syntaxin 5 (Sed5p) Vti1p Vam3p Clathrin Yip1p-Yif1p Syntaxin 11 Ykt6p Sec13 5 Rab7 (Ypt7p) GTP Reversible

all Rab proteins interact with the GDI SEC22b (Sec22p) Syntaxin 7 (Vam3p) tethered Sar1 * HOPS [GEF] * γ Synergin Syntaxin 8 (Vam7p) GDP vacuoles

Sec23 EAR YKT6 (Ykt6p) GDP Rab1 programming donor membrane RILP [Rab7 effector, dynein-dynactin Myosin Va LMA1 recruitment factor] BET1 (Bet1p) Vps33 (Vps33p,11p,18p,16p) Sar1 COP II p115 (Uso1p) Vam3p,7p LMA1 vesicle Gyp2p,3p,4p,6p,7p [GAPs] GTP 5 * Vam2/6 Sec12 GTP 1 GM130 Nyv1p Ypt7 Vam7 Sec24 1 Vam2p,6p [R-SNAREs] p Slac2a/melanophilin G Vtilp A Giantin Arf1 T GGAs (Ggas) GDP GAP GDI p115 p28/GOS28 (Gos1p) GDP Rab1 7 Syntaxin3 GTP 6 Rab6a,b (Ypt6p) Rab27 LMA1 Rab1 GTP V GAP SHD VAMP1,2 (Snc1p,2p) Arf1 H Rabkinesin6 [MT binding protein] Cargo GEF S GEF Rab6-KIFL Munc18 (Sec1p) GTP GTP 3 Syntaxin 5 (Sed5p) GAPcenA [GAP] Melanosome SNAP23 (Sec9p) trans-SNARE Membrin (Bos1p) priming ER Ric1p/Rgp1 p [GEF] Gos28 (p28) (Vps53p,55p,54p) (Yp16p-binding protein) VAMP4 8 Proposed model for vesicles docking and fusion COPII coat consists of Sar1, Sec23/24, Sec13/31 Rab9 SNAP29 (Spo20p) RabGTP Sec12 [GEF] CI-MPR Tip47 11 Sec4p YKT6 (Ykt6p) Tethering 2 Rab1 programming acceptor membrane Rab11 Dss4p protein Sec23/24 [GAP] Sft1p (R-SNARE) Rabphilin11 Sec3p,8p,5p,6p,10p,15p NSF 4 Assembly of AP1-containing coats at the TGN: α SNAP Sec2p [GEF] VAMP2 α SNAP the AP1 proteins (γ1/2, β1, µ1A/1B, δ1A/1B/1C) Golgi : CGN Gyp1p,2p,3p,4p [GAP] 2 NSF are recruited by Arf1–GTP and in turn recruit GTP 7 Rab11a,11b (Ypt31p/32p) Syntaxin 6 (Tlg1p) GDP ATP ADP+Pi GTP Rab8 4 Munc18 Rab11BP Syntaxin10 clathrin and accessory proteins. Rab8IP [stress-activated protein]

Arf1 Arf GRASP65 TRAPP (TRAPP) [GEF] Syntaxin11 GAP GM130 5 Mss4 Munc18

GAP COPI 6 Eferin

GDP GTP P Syntaxin16 (Tig2p)

S Fip2 [Rab8 effector]

A 0

R Rabphilin11

1 VTi1 (Vti1p)

or Arf1 or G Rab11 Arf1 Arf1 M

p200 GTP GTP GTP G Rab11 FIPI-3 [Rab11 effector] Snc1p,2p Pp75/Rip11 8 Rab3a Syntaxin1a SNARE GRASP65 Eferin (Q-SNARE) complex Golgi-derived GM130 Rabaptin5 [Rab5/4-binding protein] Rabphilin 11 Syntaxin 7 (Vam3p)

SNAP25 Syntaxin 1a,b (Sso1p,2p) Cargo vesicle GTP Rabphilin [α-actinin-binding protein] TRIP 8b 5 Syntaxin 8 (Vam7p) VAMP1,2 RIM1,2 [RIM-BP1-binding protein] Vti1 (Vti1p) 2+ 12 Rab2 may be involved SNAP25 (Sec9p) Calmodulin [Ca sensor] Cellubrevin (Snc1p,2p) -synergin-s in COPI recruitment γ Rabin-3 [GEF] Munc18 (Sec1p) COPI coat consists of α, β, β', γ, ε, δ, ζ subunits VAMP7,8 (Nyv1p) β1 γ Rab3-GAP [GAP] NSF (Sec18p) p200 (Sec7p, Gea1p, Gea2p) [GEF] 3 IC assembly: macromolecular complex 13 Rab33p Endobrevin 9 Syntaxin 1(Sso1p,2p) 10 Syntaxin 18 (Ufe1p) α-SNAP (Sec17p) GM130 Vps45 (Vps45p) µ Rabaptin 5 Syntaxin 2 Sec20p 1 δ1 p115 Vps33 (Vps33p) 9 Rab3b,c,d Rabex 5 Syntaxin 3 Sec22p GTP Rabphilin Spo20p Cargo Arf1 14 Syntaxin 4 GTP GM130 RIM1,2 Rab11 VAMP5,6 5 Arf1 protein Rip11 [Rab11 effector] 6 Arf1 Calmodulin SNAP23 (Sec9p) δ β COP II GRASP65 GTP Rabin-3 Eferin [Rab11 effector] AP3: , 3A/3B, AP4 vesicle Cellubrevin (Snc1p,2p) Rab3-GAP RCP [Rab11, Rab4 effector] µ3A/3B, δ3A/3B Clathrin? 15 Rab2 Clathrin Golgi-derived vesicle GRASP55-golgin 45

(See poster insert) 1780 Journal of Cell Science 115 (9) the cis compartment of the Golgi family GTPases (middle panel). The Rab chaperones to mediate conformational apparatus. protein family now includes at least 63 rearrangements coordinated with the isoforms in mammals and 11 in yeast. activity of other regulatory proteins and COPI coat assembly on the IC and All Rab proteins are found in the cytosol signaling molecules such as Ca2+. Rab subsequent Golgi compartments is in the GDP-state complexed with GTPases are likely to play critical role in regulated by the ARF1 GTPase, which Rab guanine nucleotide dissociation the ordered assembly of these tethering- promotes the recruitment of the cytosolic inhibitor (GDI). The Rab-GDI complex fusion complexes. Therefore, the COP complex (left panel), containing delivers each Rab GTPase to a sequential assembly of vesicle coats that seven different subunits. ARF1 also different membrane compartment during direct cargo selection (left panel) and participates in the activation of lipid formation of transport intermediates, and recruitment of the targeting (middle kinase signaling pathways involving here they are activated by Rab-speciﬁc panel) and fusion (right panel) PLD that regulate Golgi structure and GEFs. Activated Rabs subsequently machinery culminates in the formation function. Cargo moves through the recruit a wide variety of effectors that of a biochemical machine that dictates Golgi stack in a cis-to-trans direction by can mediate (1) vesicle motility through the speciﬁc trafficking of proteins a mechanism that is likely to involve linkage to kinesin and myosin motors through the exocytic pathway. directed maturation. In this process, and/or (2) direct the tethering of Golgi-resident proteins are sequentially transport intermediates to their target Abbreviations used: ARF, ADP-ribosylation retrieved from more terminal, mature membranes. In ER-to-Golgi transport, factor; CI-MPR, cation-independent mannose 6- phosphate receptor; COPI, coat-binding complex I; compartments using the COPI retrieval the Rab1 GTPase found on COPII- COPII, coat-binding complex II; GDI, guanine pathway, whereas cargo is collected at derived tubules/vesicles recruits the dissociation inhibitor; GEF; guanine nucleotide the trans face. Here, cargo proteins are tether molecule p115, which targets the exchange factor; GAP, GTPase-activating protein; sorted to a variety of different intermediate to Golgi membranes GGAs, Golgi-localized, γ-ear-containing ARF- binding proteins; GM130, Golgi matrix protein destinations. Some will be transported containing the cognate tether complex 130; GRASP-65, Golgi reassembly stacking to the plasma membrane using the GM130-GRASP65. protein 65; PI4K, phosphatidylinositol 4-kinase; constitutive pathway, others are sorted HOPS, homotypic fusion and vacuole protein via regulated pathways to, for example, Vesicle fusion is facilitated by the sorting; MT, microtubule; NSF, N- secretory granules, secretory lysosomes, activity of SNARE proteins (right ethylmaleimide-sensitive factor; PLD, phospholipase D; Rab11BP, Rab11-binding such as melanosomes found in panel). Fusion requires the formation of protein; RCP, Rab coupling protein; RILP, Rab- melanocytes, or synaptic vesicles that trans SNARE complexes that contain at interacting lysosomal protein; SNAP, soluble N- release neurotransmitter at the synapse. least one R-SNARE, which is usually ethylmaleimide fusion protein attachment protein; In addition, proteins can be transported found on the carrier intermediate (often v/t-SNARE, vesciular (v)- and target (t)-soluble NSF attachment protein receptors; Vam, vacuolar to endosomes, late endosomes referred to as the vesicle-associated or morphology; Vps, vacuolar protein sorting; (prevacuoles in yeast) and to lysosomes v-SNARE, such as VAMP1, which is TRAPP, transport protein particle. (vacuoles in yeast). These pathways found on synaptic vesicles involved in utilize ARF1 (or, potentially, other ARF neurotransmitter release) and several isoforms), clathrin and adaptor proteins target-membrane-associated Q-SNAREs (AP 1-4) and GGAs to facilitate cargo (or t-SNAREs, such as syntaxin and Cell Science at a Glance on the Web segregation into distinct vesicle and SNAP25 proteins, found on the Electronic copies of the poster insert are tubule intermediates that direct cargo presynaptic membrane). The assembly available in the online version of this article along their respective pathways. of trans SNARE complexes requires at jcs.biologists.org. The JPEG images can α be downloaded for printing or use as general factors such as NSF and - slides. Vesicle targeting is mediated by Rab SNAP that function as molecular

Year 2002 Travelling Fellowships JCS offers fellowships of up to US$4000 to graduate students and post-docs wishing to make collaborative visits to other laboratories. These are designed to cover the cost of travel and other expenses, and there is no restriction on nationality. Applicants should be working in the ﬁeld of cell biology and intend to visit a laboratory in another country. Each application is judged on the excellence of the candidate, and the importance and innovative quality of the work to be done. Application forms can be downloaded from our Web site at http://jcs.biologists.org. Please send the completed application form to the Production Editor at the address below. Journal of Cell Science Editorial Office, The Company of Biologists Limited, Bidder Building, 140 Cowley Road, Cambridge CB4 0DL, UK Deadline: 30 June 2002