Reactome | TGN-lysosomal vesicle coat assembly

TGN-lysosomal vesicle coat assembly

Stable Identifier

R-HSA-2130619

Type

Reaction [uncertain]

Species

Homo sapiens

Compartment

trans-Golgi network membrane, Golgi membrane, cytosol

ReviewStatus

5/5

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The trans-Golgi network (TGN) is the sorting and package centre for trafficking cargo to the endoplasmic reticulum, plasma membrane and endosomes. Signal peptides determine the sorting and trafficking of proteins to the endosomal-lysosomal pathway or to the cell surface. The main signals that mediate targeting of MHC-II molecules to the endocytic pathway are two dileucine-based motifs, Leu23-Ile24 and Pro31-Leu33 present in the short cytoplasmic tail of Ii (Odorizzi et al. 1994). These motifs bind both the adaptor proteins AP-1 and AP-2, which are components of clathrin coats associated with the TGN/endosomes and the plasma membrane, respectively (McCormick et al. 2005). The precise pathway of class II:Ii complex trafficking from TGN to endocytic pathway is not well understood. In one view MHC II:Ii complexes directly traffic from the TGN to lysosomes, possibly using AP-1 dependent endocytic vesicles (Peters et al. 1991, Amigorena et al. 1994). Alternatively trafficking occurs via transient expression on the cell surface followed by rapid internalization and delivery to endocytic compartments. Early immunoelectron microscopy data has shown the presence of MHC class II:Ii complex molecules primarily in TGN and lysosomes (Peters et al. 1991, Hiltbold & Roche 2002). This theory was further supported by a study examining the trafficking of sulphate-tagged class II molecules, which concluded that the rapid appearance of these molecules in lysosomes was consistent with their direct transport from the TGN to lysosomes (Hiltbold & Roche 2002, Davidson 1999). The transport of cargo MHC II:Ii complexes from the TGN to lysosomes may be mediated by small TGN vesicles coated with AP-1 and clathrin. The di-leucine-based sorting signal in the Ii cytoplasmic chain recruits AP-1 and clathrin from cytosol to TGN to form AP-1 clathrin-coated TGN-derived vesicles. This process is regulated by the small GTPase ARF-1 (Salamero et al. 1996).

Literature References

PubMed ID	Title	Journal	Year
7650016	A role for acidic residues in di-leucine motif-based targeting to the endocytic pathway Peterson, PA, Tainer, JA, Pond, L, Schutze, MP, Jackson, MR, Teyton, L, Kuhn, LA	J Biol Chem	1995
10480952	Direct transport of newly synthesized HLA-DR from the trans-Golgi network to major histocompatibility complex class II containing compartments (MIICS) demonstrated using a novel tyrosine-sulfated chimera Davidson, HW	J Biol Chem	1999
8939989	Expression of major histocompatibility complex class II molecules in HeLa cells promotes the recruitment of AP-1 Golgi-specific assembly proteins on Golgi membranes Goud, B, Hoflack, B, Salamero, J, Le Borgne, R, Saudrais, C	J Biol Chem	1996
7592972	Structure-activity relationship of the leucine-based sorting motifs in the cytosolic tail of the major histocompatibility complex-associated invariant chain Morelli, MA, Frank, RW, Saviano, G, Bremnes, B, Motta, A, Bakke, O	J Biol Chem	1995
9497313	Medium chains of adaptor complexes AP-1 and AP-2 recognize leucine-based sorting signals from the invariant chain Rodionov, DG, Bakke, O	J Biol Chem	1998
10593899	The leucine-based sorting motifs in the cytoplasmic domain of the invariant chain are recognized by the clathrin adaptors AP1 and AP2 and their medium chains Dobberstein, B, Rodionov, D, von Figura, K, Höning, S, Bakke, O, Hofmann, MW	J Biol Chem	1999
14731593	Targeting of membrane proteins to endosomes and lysosomes Sandoval, IV, Bakke, O	Trends Cell Biol	1994
2121367	MHC class II-associated invariant chain contains a sorting signal for endosomal compartments Dobberstein, B, Bakke, O	Cell	1990