The Arf GEF GBF1 is required for GGA recruitment to Golgi membranes

Stephane Lefrançois, Peter J. McCormick

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The lysosomal trafficking of the mannose 6-phosphate receptor and sortilin require that the Golgi-localized, γ-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.
Original languageEnglish
Pages (from-to)1440-1451
Number of pages12
JournalTraffic
Volume8
Issue number10
DOIs
Publication statusPublished - 1 Oct 2007

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