The GGAs pick up their coat

Abstract

Intracellular transport in the secretory and endocytic pathways involves the regulated assembly of cytoplasmic coat proteins on appropriate donor membranes. ARF proteins, constituting a family of small GTPases, are crucial for the membrane recruitment of coat proteins such as COP I and the adaptor complexes AP-1, AP-3 and AP-4. ARFs cycle between a GDP-bound, cytosolic form and a GTP-bound, active form that is associated with membranes. The ARF GTP–GDP cycle is regulated by GDP–GTP exchange factors (GEFs) that load ARFs with GTP and by GTPase-activating proteins (GAPs) that induce hydrolysis of GTP bound to ARFs, but the mechanistic details of this regulation remain sketchy. GGAs (Golgi-associated, γ-adaptin homologous, ARF-interacting proteins) constitute a recently discovered family of conserved proteins that associate with membranes of the trans-Golgi network (TGN) and are implicated in regulating ARF-dependent trafficking events 1xThe GGAs promote ARF-dependent recruitment of clathrin to the TGN. Puertollano, R. et al. Cell. 2001; 105: 93–102Abstract | Full Text | Full Text PDF | PubMed | Scopus (185)See all References, 2xA family of proteins with γ-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome. Hirst, J. et al. J. Cell Biol. 2000; 149: 67–79Crossref | PubMed | Scopus (242)See all References, 3xA selective transport route from Golgi to late endosomes that requires the yeast GGA proteins. Black, M. and Pelham, H. J. Cell Biol. 2000; 151: 587–600Crossref | PubMed | Scopus (110)See all References. In yeast, deletion of both the genes encoding GGAs results in missorting of the vacuolar enzyme carboxypeptidase Y and of the yeast syntaxin Pep12p, and a defective vacuolar morphology phenotype 2xA family of proteins with γ-adaptin and VHS domains that facilitate trafficking between the trans-Golgi network and the vacuole/lysosome. Hirst, J. et al. J. Cell Biol. 2000; 149: 67–79Crossref | PubMed | Scopus (242)See all References, 3xA selective transport route from Golgi to late endosomes that requires the yeast GGA proteins. Black, M. and Pelham, H. J. Cell Biol. 2000; 151: 587–600Crossref | PubMed | Scopus (110)See all References.Mammalian and yeast GGAs have a modular structure, comprising a VHS, GAT, hinge and γ-adaptin ear domain. The GAT domain of the GGAs binds directly to the GTP-bound form of several members of the ARF family and is sufficient to target a GFP reporter protein to the Golgi complex. The VHS domain is implicated in interactions with vesicle cargo. Puertollano et al. have now performed a structure–function analysis of the GAT and hinge domains of GGAs, focusing on human GGA3 1xThe GGAs promote ARF-dependent recruitment of clathrin to the TGN. Puertollano, R. et al. Cell. 2001; 105: 93–102Abstract | Full Text | Full Text PDF | PubMed | Scopus (185)See all