{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n ARL1 is an Arf‐like small GTPase that primarily localizes to the trans‐Golgi network, where it plays a central role in ensuring proper vesicular trafficking and Golgi function. Structural studies have shown that ARL1 directly interacts with the dimerization and cyclophilin binding (DCB) domain of Golgi-localized guanine nucleotide exchange factors (GEFs) such as BIG1, which is critical for targeting these factors to the Golgi and for appropriate activation of Arf1-dependent processes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, ARL1’s activity is modulated by specific GAP proteins; for example, ArfGAP1 has been demonstrated to stimulate GTP hydrolysis on ARL1, thereby regulating its membrane association and function during vesicle trafficking at the trans‐Golgi network."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Studies in Leishmania highlight an evolutionarily conserved role for ARL1, where its proper nucleotide-dependent cycling is essential for endocytosis and intracellular trafficking from the trans‐Golgi network to downstream compartments, reinforcing the importance of this GTPase in membrane dynamics."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Beyond its classical role in membrane trafficking, ARL1 expression is differentially regulated by signaling pathways; for instance, its levels are modulated in response to specific MAP kinase kinase isoforms, suggesting that ARL1 may serve as an integrator of signaling and vesicular transport."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n ARL1 has also been implicated in lipid homeostasis. It is one of two small GTPases known to influence the biogenesis and function of lipid droplets and chylomicrons through effects on Golgi-associated proteins such as Golgins and Rab proteins, thereby contributing to membrane lipid organization and transport"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": ";."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In yeast, overexpression of ARL1 confers resistance to agents that compromise membrane integrity, underscoring its role in maintaining proper membrane trafficking and cellular homeostasis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "7"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Its consistently stable expression, as demonstrated by comparative transcriptome analyses, has even led to the proposition of ARL1 as a reliable reference gene in various expression studies."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Comparative sequence analyses further place ARL1 within the continuum of Arf/Arl GTPases, revealing unique conserved residues that likely contribute to its specialized regulatory mechanisms in vesicle formation, targeting, and nucleotide cycling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": " In vitro biochemical comparisons also indicate that, despite sharing some functional similarities with canonical ARF1, ARL1 exhibits distinct activities regarding phospholipase D activation and nucleotide binding, which may underlie its unique cellular roles."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Antonio Galindo, Nicolas Soler, Stephen H McLaughlin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Structural Insights into Arl1-Mediated Targeting of the Arf-GEF BIG1 to the trans-Golgi."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Rep (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.celrep.2016.06.022"}], "href": "https://doi.org/10.1016/j.celrep.2016.06.022"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27373159"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27373159"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Hsiang-Pu Feng, Hsiao-Yun Cheng, Ting-Feng Hsiao, et al. "}, {"type": "b", "children": [{"type": "t", "text": "ArfGAP1 acts as a GTPase-activating protein for human ADP-ribosylation factor-like 1 protein."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FASEB J (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1096/fj.202000818RR"}], "href": "https://doi.org/10.1096/fj.202000818RR"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33715220"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33715220"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Annelise Sahin, Benoît Espiau, Emmanuel Tetaud, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The leishmania ARL-1 and Golgi traffic."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0001620"}], "href": "https://doi.org/10.1371/journal.pone.0001620"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18286177"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18286177"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "G Pacheco-Rodriguez, J Moss, M Vaughan "}, {"type": "b", "children": [{"type": "t", "text": "Preparation and assay of recombinant ADP-ribosylation factor-like protein-1 (ARL1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Methods Enzymol (2001)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/s0076-6879(01)29103-4"}], "href": "https://doi.org/10.1016/s0076-6879(01"}, {"type": "t", "text": "29103-4) PMID: "}, {"type": "a", "children": [{"type": "t", "text": "11210562"}], "href": "https://pubmed.ncbi.nlm.nih.gov/11210562"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Rosa L Lopez-Marques, Lisa Theorin, Michael G Palmgren, et al. "}, {"type": "b", "children": [{"type": "t", "text": "P4-ATPases: lipid flippases in cell membranes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Pflugers Arch (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1007/s00424-013-1363-4"}], "href": "https://doi.org/10.1007/s00424-013-1363-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24077738"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24077738"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Deike Hesse, Alexander Jaschke, Bomee Chung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Trans-Golgi proteins participate in the control of lipid droplet and chylomicron formation."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biosci Rep (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1042/BSR20120082"}], "href": "https://doi.org/10.1042/BSR20120082"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23033902"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23033902"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Maria D L A Jaime, Luis Vicente Lopez-Llorca, Ana Conesa, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of yeast genes that confer resistance to chitosan oligosaccharide (COS) using chemogenomics."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "BMC Genomics (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1471-2164-13-267"}], "href": "https://doi.org/10.1186/1471-2164-13-267"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22727066"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22727066"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Sang-Je Park, Young-Hyun Kim, Jae-Won Huh, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Selection of new appropriate reference genes for RT-qPCR analysis via transcriptome sequencing of cynomolgus monkeys (Macaca fascicularis)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0060758"}], "href": "https://doi.org/10.1371/journal.pone.0060758"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23613744"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23613744"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Andrew F Neuwald "}, {"type": "b", "children": [{"type": "t", "text": "Bayesian classification of residues associated with protein functional divergence: Arf and Arf-like GTPases."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Direct (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/1745-6150-5-66"}], "href": "https://doi.org/10.1186/1745-6150-5-66"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21129209"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21129209"}]}, {"type": "r", "ref": 10, "children": [{"type": "t", "text": "J X Hong, F J Lee, W A Patton, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Phospholipid- and GTP-dependent activation of cholera toxin and phospholipase D by human ADP-ribosylation factor-like protein 1 (HARL1)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (1998)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.273.25.15872"}], "href": "https://doi.org/10.1074/jbc.273.25.15872"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "9624189"}], "href": "https://pubmed.ncbi.nlm.nih.gov/9624189"}]}]}]}