{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARFRP1 is a small GTPase that predominantly localizes to the trans‐Golgi network where it orchestrates multiple aspects of intracellular trafficking. In this central role, ARFRP1 governs the recruitment and activation of other ARF‐like GTPases (such as ARL1 and ARL5) and their effector proteins (including GRIP domain golgins), thereby ensuring proper sorting of cargo proteins and the formation of specific transport vesicles."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": "\n This regulation is critical for diverse cellular functions, ranging from the retrograde transport of toxins and the correct cell surface delivery of adhesion molecules like E‐cadherin to the assembly of SNARE complexes that underpin vesicular fusion events.\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition to its pivotal role in protein sorting, ARFRP1 has emerged as an important regulator of lipid metabolism. In intestinal epithelial cells and hepatocytes, ARFRP1 is essential for the lipidation and assembly of lipoprotein particles – chylomicrons and very low‐density lipoproteins respectively – thereby influencing systemic lipid levels and energy homeostasis."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "8"}]}, {"type": "t", "text": "\n In adipose tissue and skeletal muscle, ARFRP1 also modulates lipid droplet growth and lipolysis, and it plays a role in the proper targeting of glucose transporters such as GLUT4, with implications for metabolic regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond these functions, ARFRP1 participates in specialized secretory processes. For instance, it contributes to the regulation of insulin secretion in pancreatic β‐cells by influencing the localization and stability of SNARE proteins such as SNAP25"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", and it facilitates hepatitis C virus propagation by modulating lipid droplet dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Moreover, altered ARFRP1 expression in the brain has been associated with changes following sleep deprivation, and genetic variations in the ARFRP1 locus may be linked to body mass index variations, underscoring its broader physiological relevance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these studies demonstrate that ARFRP1 functions as a master regulator of vesicular trafficking at the Golgi, integrating pathways that control protein sorting, cell adhesion, lipoprotein assembly, glucose and lipid metabolism, and even hormone secretion. The multifaceted roles of ARFRP1 thereby underpin normal development and metabolic homeostasis while also contributing to the pathogenesis of diverse human diseases."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "4"}, {"type": "fg_f", "ref": "9"}, {"type": "fg_fs", "start_ref": "6", "end_ref": "8"}, {"type": "fg_f", "ref": "10"}, {"type": "fg_f", "ref": "13"}, {"type": "fg_f", "ref": "12"}, {"type": "fg_f", "ref": "14"}, {"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hye-Won Shin, Hiromi Kobayashi, Masashi Kitamura, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Roles of ARFRP1 (ADP-ribosylation factor-related protein 1) in post-Golgi membrane trafficking."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Sci (2005)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1242/jcs.02524"}], "href": "https://doi.org/10.1242/jcs.02524"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "16129887"}], "href": "https://pubmed.ncbi.nlm.nih.gov/16129887"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Claudia Zahn, Angela Hommel, Lei Lu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Knockout of Arfrp1 leads to disruption of ARF-like1 (ARL1) targeting to the trans-Golgi in mouse embryos and HeLa cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Membr Biol (2006)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1080/09687860600840100"}], "href": "https://doi.org/10.1080/09687860600840100"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "17127620"}], "href": "https://pubmed.ncbi.nlm.nih.gov/17127620"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Kirika Nishimoto-Morita, Hye-Won Shin, Hiroko Mitsuhashi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Differential effects of depletion of ARL1 and ARFRP1 on membrane trafficking between the trans-Golgi network and endosomes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2009)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M900847200"}], "href": "https://doi.org/10.1074/jbc.M900847200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "19224922"}], "href": "https://pubmed.ncbi.nlm.nih.gov/19224922"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Claudia Zahn, Alexander Jaschke, Jörg Weiske, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ADP-ribosylation factor-like GTPase ARFRP1 is required for trans-Golgi to plasma membrane trafficking of E-cadherin."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M802108200"}], "href": "https://doi.org/10.1074/jbc.M802108200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18662990"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18662990"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Morié Ishida, Juan S Bonifacino "}, {"type": "b", "children": [{"type": "t", "text": "ARFRP1 functions upstream of ARL1 and ARL5 to coordinate recruitment of distinct tethering factors to the trans-Golgi network."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Cell Biol (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1083/jcb.201905097"}], "href": "https://doi.org/10.1083/jcb.201905097"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31575603"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31575603"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Alexander Jaschke, Bomee Chung, Deike Hesse, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The GTPase ARFRP1 controls the lipidation of chylomicrons in the Golgi of the intestinal epithelium."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Mol Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/hmg/dds140"}], "href": "https://doi.org/10.1093/hmg/dds140"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22505585"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22505585"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Deike Hesse, Katrin Radloff, Alexander Jaschke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Hepatic trans-Golgi action coordinated by the GTPase ARFRP1 is crucial for lipoprotein lipidation and assembly."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Lipid Res (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1194/jlr.M040089"}], "href": "https://doi.org/10.1194/jlr.M040089"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24186947"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24186947"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Deike Hesse, Alexander Jaschke, Timo Kanzleiter, et al. "}, {"type": "b", "children": [{"type": "t", "text": "GTPase ARFRP1 is essential for normal hepatic glycogen storage and insulin-like growth factor 1 secretion."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.00522-12"}], "href": "https://doi.org/10.1128/MCB.00522-12"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22927645"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22927645"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Angela Hommel, Deike Hesse, Wolfgang Völker, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ARF-like GTPase ARFRP1 is essential for lipid droplet growth and is involved in the regulation of lipolysis."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Cell Biol (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1128/MCB.01269-09"}], "href": "https://doi.org/10.1128/MCB.01269-09"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20038528"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20038528"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "Deike Hesse, Angela Hommel, Alexander Jaschke, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Altered GLUT4 trafficking in adipocytes in the absence of the GTPase Arfrp1."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2010.03.059"}], "href": "https://doi.org/10.1016/j.bbrc.2010.03.059"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20230794"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20230794"}]}, {"type": "r", "ref": 11, "children": [{"type": "t", "text": "Jeffrey D Covington, Jose E Galgani, Cedric Moro, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Skeletal muscle perilipin 3 and coatomer proteins are increased following exercise and are associated with fat oxidation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0091675"}], "href": "https://doi.org/10.1371/journal.pone.0091675"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24632837"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24632837"}]}, {"type": "r", "ref": 12, "children": [{"type": "t", "text": "Ilka Wilhelmi, Stephan Grunwald, Niclas Gimber, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The ARFRP1-dependent Golgi scaffolding protein GOPC is required for insulin secretion from pancreatic β-cells."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Mol Metab (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.molmet.2020.101151"}], "href": "https://doi.org/10.1016/j.molmet.2020.101151"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33359402"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33359402"}]}, {"type": "r", "ref": 13, "children": [{"type": "t", "text": "Yun-Sook Lim, Huong T T Ngo, Jihye Lee, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ADP-ribosylation Factor-related Protein 1 Interacts with NS5A and Regulates Hepatitis C Virus Propagation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/srep31211"}], "href": "https://doi.org/10.1038/srep31211"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27550144"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27550144"}]}, {"type": "r", "ref": 14, "children": [{"type": "t", "text": "S Paratore, R Parenti, S Cavallaro "}, {"type": "b", "children": [{"type": "t", "text": "Distribution of ADP-ribosylation factor-related protein 1 in mouse brain."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Arch Ital Biol (2008)"}]}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18666447"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18666447"}]}]}]}