Pathway Map Details
Transport_Clathrin-coated vesicle cycle
Object list (links open in MetaCore):
GDI2, GOS-28, Rip11, GS15, VPS45A, YKT6, 1-(1,2-diacyl-glycerol 3-phospho)-inositol 3-phosphate, Actin cytoskeletal, PI3K cat class III, Rabenosyn-5, ARF1, Myosin Vb, RABGEF1, Rabaptin-5, DAB2, Syntaxin 12, Actin, Optineurin, BIN1 (Amphiphysin II), VAMP7, PIP5KIII, Clathrin, VAMP4, Rab-11A, SNAP-25, Myosin I, AP180, AP complex 2, Rab-8, SAR1A, HIP12, 18.104.22.168, Myosin VI, HIP1, Clathrin heavy chain, PI3K cat class III, GCC2, ATP + 1,2-diacyl-glycerol 3-phosphoinositol = ADP + 1-(1,2-diacyl-glycerol 3-phospho)-inositol 3-phosphate, 1,2-diacyl-glycerol 3-phosphoinositol, Rab11-FIP1, VAMP8, Epsin 1, Syntaxin 5, Rab11-FIP2, PREB, VTI1B, COPII, Rab-9, NSF, 1-(1,2-diacyl-glycerol 3-phospho)-inositol 3-phosphate, Rabaptin-5, Syntaxin 16, Rab-7, RABGDIA, AP complex 1, Syntaxin 7, PLEKHA8 (FAPP2), Eps15, VAMP2, Rab-5A, Actin cytoskeletal, Rab-7, Endophilin B1, Rab-4, Rabenosyn-5, VTI1A, SNX9, TIP47, PI3K reg class III, Syntaxin 6, PI3K reg class III, Myosin VI, RAB9P40, RILP, Dynamin-2, 1,2-diacyl-glycerol 3-phosphoinositol, EEA1, SAR1, Syntaxin 8, PICALM, Coatomer
Clathrin-coated vesicle cycle
Transport vesicles are classified according to the components of the protein coat that surrounds them during their genesis and early life. One of the most common and probably best-characterized classes of coated vesicle is that comprising three-layered Clathrin -coated vesicles (CCVs). CCVs are so-called because the main component of the coat is complex Clathrin, which forms a polymeric mechanical scaffold on the vesicle surface. The inner, membrane layer with its embedded cargo is linked to the outer, Clathrin layer by a middle layer that consists of various clathrin-adaptor molecules and other proteins that have accessory/regulatory roles in CCV assembly. The classical key components of absolute majority cargos Clathrin-dependent endocytosis are Adaptor-related protein complex 2 ( AP complex 2 ), Epidermal growth factor receptor pathway substrate 15 ( Eps15 ), Synaptosomal-associated protein 91kDa homolog ( AP180 ), Epsin 1, Huntingtin interacting protein 1 ( HIP1 )/ Huntingtin interacting protein 1 related ( HIP12 ) and others , , .
After the Clathrin lattice is formed, dynamins (e.g., Dynamin-2 ), endophilin (e.g., Endophilin B1 ), epsins and amphiphysin (e.g., BIN1 ) are involved in membrane invagination and Clathrin rearrangements. The plus-end motor Myosin I pulls the Dynamin-2 ring in the direction of the cell surface, while the minus-end motor Myosin VI pulls the coated bud into the cytosol. The resulting strain could then sever the constricted stalk beneath the dynamin ring .
Next phase is a fusion of coated-pit-derived primary endocytic vesicles with sorting endosomes. It is regulated by member RAS oncogene family Rab-5A, Early endosome antigen 1 ( EEA1 ) , ,  and Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) , .
Late endosomes may participate in fusion to other late endosomes or lysosome via SNARE-mediated mechanism. Combinatorial SNARE complexes with Synaptobrevin-like 1 ( VAMP7 ) or Vesicle-associated membrane protein 8 ( VAMP8 ) define these different late endocytic fusion events, accordingly , , .
Then, cargo may be delivered to the Golgi from late endosomes with participation RAS oncogene family Rab-9 , , . In addition, proteins from endoplasmic reticulum may be translocated to the Golgi in Coat protein complex-II ( COPII )-dependent manner .
Modified in endoplasmic reticulum and/or Golgi cargo may be delivered from the Golgi back to the cell surface, possibly with participation Rab8/ Optineurin/ Myosin VI pathway , ,  and/or coat protein complex termed Coatomer , , .
Moreover, cargo may be delivered to the cell surface via shot pathway from endosomes via different recycling endosomes . It is realized mainly via Rab-4 and/or Rab-11A -dependent mechanisms , , .
- Wendland B
Epsins: adaptors in endocytosis? Nature reviews. Molecular cell biology 2002 Dec;3(12):971-7
- Szymkiewicz I, Shupliakov O, Dikic I
Cargo- and compartment-selective endocytic scaffold proteins. The Biochemical journal 2004 Oct 1;383(Pt 1):1-11
- Edeling MA, Smith C, Owen D
Life of a clathrin coat: insights from clathrin and AP structures. Nature reviews. Molecular cell biology 2006 Jan;7(1):32-44
- Ungewickell EJ, Hinrichsen L
Endocytosis: clathrin-mediated membrane budding. Current opinion in cell biology 2007 Aug;19(4):417-25
- McBride HM, Rybin V, Murphy C, Giner A, Teasdale R, Zerial M
Oligomeric complexes link Rab5 effectors with NSF and drive membrane fusion via interactions between EEA1 and syntaxin 13. Cell 1999 Aug 6;98(3):377-86
- Woodman PG
Biogenesis of the sorting endosome: the role of Rab5. Traffic (Copenhagen, Denmark) 2000 Sep;1(9):695-701
- Maxfield FR, McGraw TE
Endocytic recycling. Nature reviews. Molecular cell biology 2004 Feb;5(2):121-32
- Hong W
SNAREs and traffic. Biochimica et biophysica acta 2005 Jun 30;1744(2):120-44
- Feng Y, Press B, Wandinger-Ness A
Rab 7: an important regulator of late endocytic membrane traffic. The Journal of cell biology 1995 Dec;131(6 Pt 1):1435-52
- Somsel Rodman J, Wandinger-Ness A
Rab GTPases coordinate endocytosis. Journal of cell science 2000 Jan;113 Pt 2:183-92
- Bucci C, Thomsen P, Nicoziani P, McCarthy J, van Deurs B
Rab7: a key to lysosome biogenesis. Molecular biology of the cell 2000 Feb;11(2):467-80
- Pryor PR, Mullock BM, Bright NA, Lindsay MR, Gray SR, Richardson SC, Stewart A, James DE, Piper RC, Luzio JP
Combinatorial SNARE complexes with VAMP7 or VAMP8 define different late endocytic fusion events. EMBO reports 2004 Jun;5(6):590-5
- Stein MP, Feng Y, Cooper KL, Welford AM, Wandinger-Ness A
Human VPS34 and p150 are Rab7 interacting partners. Traffic (Copenhagen, Denmark) 2003 Nov;4(11):754-71
- Barbero P, Bittova L, Pfeffer SR
Visualization of Rab9-mediated vesicle transport from endosomes to the trans-Golgi in living cells. The Journal of cell biology 2002 Feb 4;156(3):511-8
- Aivazian D, Serrano RL, Pfeffer S
TIP47 is a key effector for Rab9 localization. The Journal of cell biology 2006 Jun 19;173(6):917-26
- G-Xrkan C, Stagg SM, Lapointe P, Balch WE
The COPII cage: unifying principles of vesicle coat assembly. Nature reviews. Molecular cell biology 2006 Oct;7(10):727-38
- Sahlender DA, Roberts RC, Arden SD, Spudich G, Taylor MJ, Luzio JP, Kendrick-Jones J, Buss F
Optineurin links myosin VI to the Golgi complex and is involved in Golgi organization and exocytosis. The Journal of cell biology 2005 Apr 25;169(2):285-95
- Au JS, Puri C, Ihrke G, Kendrick-Jones J, Buss F
Myosin VI is required for sorting of AP-1B-dependent cargo to the basolateral domain in polarized MDCK cells. The Journal of cell biology 2007 Apr 9;177(1):103-14
- Antonny B, Huber I, Paris S, Chabre M, Cassel D
Activation of ADP-ribosylation factor 1 GTPase-activating protein by phosphatidylcholine-derived diacylglycerols. The Journal of biological chemistry 1997 Dec 5;272(49):30848-51
- Godi A, Di Campli A, Konstantakopoulos A, Di Tullio G, Alessi DR, Kular GS, Daniele T, Marra P, Lucocq JM, De Matteis MA
FAPPs control Golgi-to-cell-surface membrane traffic by binding to ARF and PtdIns(4)P. Nature cell biology 2004 May;6(5):393-404
- de Renzis S, Sonnichsen B, Zerial M
Divalent Rab effectors regulate the sub-compartmental organization and sorting of early endosomes. Nature cell biology 2002 Feb;4(2):124-33
- Hales CM, Griner R, Hobdy-Henderson KC, Dorn MC, Hardy D, Kumar R, Navarre J, Chan EK, Lapierre LA, Goldenring JR
Identification and characterization of a family of Rab11-interacting proteins. The Journal of biological chemistry 2001 Oct 19;276(42):39067-75
- Mallard F, Tang BL, Galli T, Tenza D, Saint-Pol A, Yue X, Antony C, Hong W, Goud B, Johannes L
Early/recycling endosomes-to-TGN transport involves two SNARE complexes and a Rab6 isoform. The Journal of cell biology 2002 Feb 18;156(4):653-64