Abstract

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 sorting events at the TGN involve transmembrane receptors which are themselves bearing sorting determinants in their cytoplasmic tails.

The interaction of such sorting signals with adaptor proteins such as APs and GGAs is responsible for the targeting of the receptors (and therefore their cargo). The acidic di Leu signals are interacting with the VHS domains of the GGAs adaptor proteins which in turn can bind to clathrin, ARF factor (regulator of coat assembly at the TGN) and other adaptors interacting with AP-1 gamma subunit. GGAs act by recruiting the receptors into TGN-derived clathrin-coated vesicles for transport to endosomes. The juxtamembrane di Leucine signals interact with AP1, AP2, AP3 and probably AP4 in trafficking events such as endocytosis, targeting to lysosomes or specialed compartments like melanosomes.