The Arf GEF GBF1 is required for GGA recruitment to Golgi membranes.
The lysosomal trafficking of the mannose 6-phosphate receptor and sortilin require that the Golgi-localized, gamma-ear-containing, ADP ribosylation factor (Arf)-binding proteins (GGAs) be recruited to Golgi membranes where they bind a signal in the cytosolic tail of the receptors and recruit clathrin to form trafficking vesicles. GGA recruitment to membranes requires Arf1, a protein that cycles between a GDP-bound inactive state and GTP-bound active state. The guanine nucleotide exchange factors (GEFs) promote the formation of Arf-GTP, while the GTPase activating proteins induce hydrolysis of GTP to GDP. We provide evidence that the GEF, GBF1, colocalizes with the GGAs and interacts with the GGAs. Depletion of GBF1 or expression of an inactive mutant prevents recruitment of the GGAs to Golgi membranes and results in the improper sorting of cargo. In summary, we show that GBF1 is required for GGA recruitment to Golgi membranes and plays a role in the proper processing and sorting of lysosomal cargo.
Lefrançois
Stéphane
S
Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, Canada. stephane.lefrancois@umontreal.ca
McCormick
Peter J
PJ
D020823:ADP-Ribosylation Factor 1 / Q000502:physiology*; D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D033942:Adaptor Proteins, Vesicular Transport / Q000378:metabolism*; D000818:Animals; D006056:Golgi Apparatus / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008247:Lysosomes / Q000378:metabolism; D051379:Mice; D021381:Protein Transport / Q000502:physiology
C119087:ARFGEF1 protein, human; D033942:Adaptor Proteins, Vesicular Transport; C120445:GBF1 protein, human; C407306:GGA adaptor proteins; D020662:Guanine Nucleotide Exchange Factors; D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors