Redundant roles of BIG2 and BIG1, guanine-nucleotide exchange factors for ADP-ribosylation factors in membrane traffic between the trans-Golgi network and endosomes.
BIG2 and BIG1 are closely related guanine-nucleotide exchange factors (GEFs) for ADP-ribosylation factors (ARFs) and are involved in the regulation of membrane traffic through activating ARFs and recruiting coat protein complexes, such as the COPI complex and the AP-1 clathrin adaptor complex. Although both ARF-GEFs are associated mainly with the trans-Golgi network (TGN) and BIG2 is also associated with recycling endosomes, it is unclear whether BIG2 and BIG1 share some roles in membrane traffic. We here show that knockdown of both BIG2 and BIG1 by RNAi causes mislocalization of a subset of proteins associated with the TGN and recycling endosomes and blocks retrograde transport of furin from late endosomes to the TGN. Similar mislocalization and protein transport block, including furin, were observed in cells depleted of AP-1. Taken together with previous reports, these observations indicate that BIG2 and BIG1 play redundant roles in trafficking between the TGN and endosomes that involves the AP-1 complex.
Ishizaki
Ray
R
Graduate School of Pharmaceutical Sciences, Kyoto University, Kyoto 606-8501, Japan.
Shin
Hye-Won
HW
Mitsuhashi
Hiroko
H
Nakayama
Kazuhisa
K
D020727:ADP-Ribosylation Factors / Q000378:metabolism*; D033961:Adaptor Protein Complex 1 / Q000378:metabolism; D000595:Amino Acid Sequence; D015704:CD4 Antigens / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D045683:Furin / Q000737:chemistry / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008954:Models, Biological; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D021381:Protein Transport; D011990:Receptors, Transferrin / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism*
C119087:ARFGEF1 protein, human; C119088:ARFGEF2 protein, human; D033961:Adaptor Protein Complex 1; D015704:CD4 Antigens; D020662:Guanine Nucleotide Exchange Factors; D011990:Receptors, Transferrin; D045683:Furin; D020727:ADP-Ribosylation Factors