TRG_LysEnd_GGAAcLL_2

Lysosomes are acidic compartments within cells where lumenal hydrolases degrade endogenous and internalized macromolecules. Most soluble hydrolases transit by the Trans Golgi network (TGN) where they are sorted from secretory proteins before they are directed to the endosome and then the lysosomes.

The trans Golgi network is a major site of membrane protein sorting. The sorting events at the TGN involve transmembrane receptors bearing sorting determinants in their cytoplasmic tails. The interaction of such sorting signals with adaptor proteins such as the GGAs (Golgi-localized, gamma ear-containing, ARF-binding protein) is responsible for the targeting of the receptors (and therefore their cargo). DxxLL acidic diLeucine signals interact with the VHS domains of the GGA adaptor proteins which in turn can bind to clathrin and ARF factor (regulator of coat assembly at the TGN). GGAs act by recruiting the receptors into TGN-derived clathrin-coated vesicles for transport to endosomes. Further sorting to lysosomes or the cell surface may then occur.

The DxxLL acidic diLeucine motifs interacting with GGAs have a very strong preference for Asp at the +1 position. This is in contrast to the acidic diLeucine motifs which bind to the sigma subunit of Adaptin-containing Adapter Protein (AP) complexes also involved in clathrin mediated vesicular transport: The AP complexes have a preference for Glu in the ExxLL acidic dileucine motifs (TRG_DiLeu_BaEn_1).