title: Differential effects of depletion of ARL1 and ARFRP1 on membrane trafficking between the trans-Golgi network and endosomes.
abstract: ARFRP1 and ARL1, which are both ARF-like small GTPases, are mammalian orthologs of yeast Arl3p and Arl1p, respectively. In yeast, Arl3p targeted to trans-Golgi network (TGN) membranes activates Arl1p, and the activated Arl1p in turn recruits a GRIP domain-containing protein; this complex regulates retrograde transport to the TGN and anterograde transport from the TGN. In the present study, using RNA interference-mediated knockdown of ARFRP1 and ARL1, we have examined whether the orthologs of Arl3p-Arl1p-GRIP story serve similar functions in mammalian cells. However, we have unexpectedly found differential roles of ARL1 and ARFRP1. Specifically, ARL1 and ARFRP1 regulate retrograde transport of Shiga toxin to the TGN and anterograde transport of VSVG from the TGN, respectively. Furthermore, we have obtained evidence suggesting that a SNARE complex containing Vti1a, syntaxin 6, and syntaxin 16 is involved in Shiga toxin transport downstream of ARL1.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, Japan.
authors.forename: Kirika
authors.initials: K
authors.lastname: Nishimoto-Morita
authors.forename: Hye-Won
authors.initials: HW
authors.lastname: Shin
authors.forename: Hiroko
authors.initials: H
authors.lastname: Mitsuhashi
authors.forename: Masashi
authors.initials: M
authors.lastname: Kitamura
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.forename: Ludger
authors.initials: L
authors.lastname: Johannes
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Nakayama
mesh_terms: D020727:ADP-Ribosylation Factors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D011992:Endosomes / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D050766:Qb-SNARE Proteins / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism; D022621:Shiga Toxin / Q000378:metabolism; D014759:Viral Envelope Proteins / Q000378:metabolism; D021601:trans-Golgi Network / Q000378:metabolism*
chemical_list: C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D050765:Qa-SNARE Proteins; D050766:Qb-SNARE Proteins; D034741:RNA, Small Interfering; D011993:Recombinant Fusion Proteins; D050600:SNARE Proteins; C491419:VTI1A protein, human; C491416:VTI1B protein, human; D014759:Viral Envelope Proteins; D022621:Shiga Toxin; C097313:ADP-ribosylation factor related proteins; D020727:ADP-Ribosylation Factors; C541296:ARFRP1 protein, human