BIG2, a guanine nucleotide exchange factor for ADP-ribosylation factors: its localization to recycling endosomes and implication in the endosome integrity.
Small GTPases of the ADP-ribosylation factor (ARF) family play a key role in membrane trafficking by regulating coated vesicle formation, and guanine nucleotide exchange is essential for the ARF function. Brefeldin A blocks the ARF-triggered coat assembly by inhibiting the guanine nucleotide exchange on ARFs and causes disintegration of the Golgi complex and tubulation of endosomal membranes. BIG2 is one of brefeldin A-inhibited guanine nucleotide exchange factors for the ARF GTPases and is associated mainly with the trans-Golgi network. In the present study, we have revealed that another population of BIG2 is associated with the recycling endosome and found that expression of a catalytically inactive BIG2 mutant, E738K, selectively induces membrane tubules from this compartment. We also have shown that BIG2 has an exchange activity toward class I ARFs (ARF1 and ARF3) in vivo and inactivation of either ARF exaggerates the BIG2(E738K)-induced tubulation of endosomal membranes. These observations together indicate that BIG2 is implicated in the structural integrity of the recycling endosome through activating class I ARFs.
Shin
Hye-Won
HW
Faculty of Pharmaceutical Sciences, Kanazawa University, Ishikawa 920-0934, Japan.
Morinaga
Naoko
N
Noda
Masatoshi
M
Nakayama
Kazuhisa
K
D020727:ADP-Ribosylation Factors / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000494:pharmacology; D015870:Gene Expression; D018698:Glutamic Acid / Q000235:genetics / Q000378:metabolism; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D009154:Mutation / Q000235:genetics; D011485:Protein Binding; D012694:Serine / Q000235:genetics / Q000378:metabolism; D022622:Shiga Toxin 1 / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism; D020695:rab4 GTP-Binding Proteins / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
D020727:ADP-Ribosylation Factors; D004815:Epidermal Growth Factor; D018698:Glutamic Acid; D020662:Guanine Nucleotide Exchange Factors; D012694:Serine; D022622:Shiga Toxin 1; D020691:rab GTP-Binding Proteins; D020695:rab4 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins