Pathway maps

Transport_Clathrin-coated vesicle cycle
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,, 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 [1], [2], [3].

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 [4].

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 ) [5], [6], [7] and Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNARE) [7], [8].

The maturation of sorting endosomes to late endosomes is realized with participation member RAS oncogene family Rab7 via unknown mechanism [9], [10].

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 [11], [12], [8].

In addition, Rab7 is directly involved in the aggregation and fusion of late endocytic structures/lysosomes [11], [13].

Then, cargo may be delivered to the Golgi from late endosomes with participation RAS oncogene family Rab-9 [10], [14], [15]. In addition, proteins from endoplasmic reticulum may be translocated to the Golgi in Coat protein complex-II ( COPII )-dependent manner [16].

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 [7], [17], [18] and/or coat protein complex termed Coatomer [19], [7], [20].

Moreover, cargo may be delivered to the cell surface via shot pathway from endosomes via different recycling endosomes [7]. It is realized mainly via Rab-4 and/or Rab-11A -dependent mechanisms [10], [21], [22].

It is shown, that recycling endosomes to Golgi traffic may be realized via different SNARE complexes [23], [7], [8].


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    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
  21. 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
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    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