title: ARF1 and ARF4 regulate recycling endosomal morphology and retrograde transport from endosomes to the Golgi apparatus.
abstract: Small GTPases of the ADP-ribosylation factor (ARF) family, except for ARF6, mainly localize to the Golgi apparatus, where they trigger formation of coated carrier vesicles. We recently showed that class I ARFs (ARF1 and ARF3) localize to recycling endosomes, as well as to the Golgi, and are redundantly required for recycling of endocytosed transferrin. On the other hand, the roles of class II ARFs (ARF4 and ARF5) are not yet fully understood, and the complementary or overlapping functions of class I and class II ARFs have been poorly characterized. In this study, we find that simultaneous depletion of ARF1 and ARF4 induces extensive tubulation of recycling endosomes. Moreover, the depletion of ARF1 and ARF4 inhibits retrograde transport of TGN38 and mannose-6-phosphate receptor from early/recycling endosomes to the trans-Golgi network (TGN) but does not affect the endocytic/recycling pathway of transferrin receptor or inhibit retrograde transport of CD4-furin from late endosomes to the TGN. These observations indicate that the ARF1+ARF4 and ARF1+ARF3 pairs are both required for integrity of recycling endosomes but are involved in distinct transport pathways: the former pair regulates retrograde transport from endosomes to the TGN, whereas the latter is required for the transferrin recycling pathway from endosomes to the plasma membrane.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Waka
authors.initials: W
authors.lastname: Nakai
authors.forename: Yumika
authors.initials: Y
authors.lastname: Kondo
authors.forename: Akina
authors.initials: A
authors.lastname: Saitoh
authors.forename: Tomoki
authors.initials: T
authors.lastname: Naito
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Nakayama
authors.forename: Hye-Won
authors.initials: HW
authors.lastname: Shin
mesh_terms: D020823:ADP-Ribosylation Factor 1 / Q000235:genetics / Q000378:metabolism*; D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D015704:CD4 Antigens / Q000378:metabolism; D045744:Cell Line, Tumor; D011992:Endosomes / Q000378:metabolism*; D045683:Furin / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D021381:Protein Transport; D034622:RNA Interference; D034741:RNA, Small Interfering; D017527:Receptor, IGF Type 2 / Q000378:metabolism; D011990:Receptors, Transferrin / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000378:metabolism; D020695:rab4 GTP-Binding Proteins / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism; D000099193:rab11 GTP-Binding Proteins
chemical_list: D020823:ADP-Ribosylation Factor 1; D020727:ADP-Ribosylation Factors; D015704:CD4 Antigens; D045683:Furin; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D017527:Receptor, IGF Type 2; D011990:Receptors, Transferrin; D020691:rab GTP-Binding Proteins; D020695:rab4 GTP-Binding Proteins; D000099193:rab11 GTP-Binding Proteins; C072237:TGOLN2 protein, human; C116687:ARF3 protein, human; C116688:ARF4 protein, human; C116691:ARF5 protein, human