RRC ID 49512
Author Ishizaki R, Shin HW, Mitsuhashi H, Nakayama K.
Title Redundant roles of BIG2 and BIG1, guanine-nucleotide exchange factors for ADP-ribosylation factors in membrane traffic between the trans-Golgi network and endosomes.
Journal Mol Biol Cell
Abstract 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.
Volume 19(6)
Pages 2650-60
Published 2008-6-1
DOI 10.1091/mbc.e07-10-1067
PII E07-10-1067
PMID 18417613
PMC PMC2397321
MeSH ADP-Ribosylation Factors / metabolism* Adaptor Protein Complex 1 / metabolism Amino Acid Sequence CD4 Antigens / metabolism Cell Membrane / metabolism Endosomes / metabolism* Furin / chemistry Furin / metabolism Guanine Nucleotide Exchange Factors / metabolism* HeLa Cells Humans Intracellular Membranes / metabolism* Models, Biological Molecular Sequence Data Mutation / genetics Phenotype Protein Transport Receptors, Transferrin / metabolism trans-Golgi Network / metabolism*
IF 3.791
Times Cited 59
DNA material pcDNA4c/His-Xpress-HA-hBIG2(WT) (RDB15364) pcDNA4c/His-Xpress-HA-hBIG2(E738K) (RDB15365).