| 1994 |
ARF1-GTP state supports the binding of coatomer (COPI) to Golgi membranes; the activating Q71I mutation slows GTP hydrolysis and stabilizes coatomer binding, providing evidence that ARF1 GTPase cycling regulates reversible coat protein association with the Golgi. |
In vitro coatomer-binding assay with GTP hydrolysis-defective ARF1 mutant (Q71I); BFA-resistance assay in cells |
The Journal of biological chemistry |
High |
8106346
|
| 1995 |
ARF1 localizes to the Golgi complex and mediates membrane recruitment of the coat proteins coatomer (COP1) and gamma-adaptin; GTP-state ARF1 is required for this association, distinct from ARF6 which acts at the endosomal/plasma membrane system. |
Transient transfection with epitope-tagged ARFs; immunofluorescence; immuno-electron microscopy; dominant-negative and constitutively active ARF mutants |
The Journal of cell biology |
High |
7896867
|
| 1995 |
An ARF1 GTPase-activating protein (GAP) was cloned from rat liver; it contains a zinc finger motif required for GAP activity, localizes to the Golgi complex, and redistributes to cytosol upon brefeldin A treatment, indicating it is recruited to the Golgi by an ARF1-dependent mechanism. |
cDNA cloning; in vitro GAP assay with zinc-finger mutants; subcellular fractionation; BFA treatment |
Science |
High |
8533093
|
| 1995 |
N-myristoylation of ARF1 (at Gly2) is required for ARF1 function in cells but not for nucleotide exchange or cofactor activities in vitro; Asp26 is essential for binding activating nucleotide GTPγS, unlike the homologous residue in Ras. |
Site-directed mutagenesis; yeast complementation; in vitro ARF activity assay |
The Journal of biological chemistry |
High |
7814365
|
| 1996 |
The giant protein p619 stimulates guanine nucleotide exchange (GEF activity) on myristoylated ARF1 and Rab proteins via its RCC1-like domain; it localizes to the Golgi in a BFA-sensitive manner and interacts specifically with myristoylated ARF1. |
In vitro nucleotide exchange assay; GST pull-down; subcellular localization; BFA treatment |
The EMBO journal |
Medium |
8861955
|
| 1997 |
The KDEL receptor ERD2 self-oligomerizes and interacts with ARF1 GAP, regulating ARF1 GAP recruitment to membranes; ERD2 overexpression enhances GAP membrane recruitment and produces an ARF1-inactivation phenotype, linking KDEL receptor signaling to ARF1 GTPase cycling. |
Co-immunoprecipitation; overexpression studies; dominant-negative ARF1 phenotype analysis |
The EMBO journal |
Medium |
9405360
|
| 2000 |
ARF1 is required for membrane recruitment of endosomal COP proteins and for in vitro biogenesis of transport intermediates destined for late endosomes; ARF1 membrane association in endosomes is regulated by endosomal pH, providing a transmembrane pH-sensing mechanism. |
In vitro endosome budding assay; cytosol fractionation; dominant-negative ARF1; pH manipulation |
The Journal of biological chemistry |
Medium |
10713138
|
| 2001 |
DEF-1/ASAP1 functions as a GAP specifically for ARF1 (not ARF6) in vivo; DEF-1-mediated ARF1 deactivation enhances cell motility in a GAP-domain-dependent manner. |
Cell-based ARF GAP assay; stable cell line overexpression; GAP-domain mutant; cell migration assay |
The Journal of biological chemistry |
Medium |
11773070
|
| 2001 |
Yeast Arf1 is involved in multiple distinct steps of intracellular transport; different temperature-sensitive arf1 alleles produce distinct transport defects and morphological alterations, demonstrating that Arf1 has separable functions at multiple trafficking steps. |
Error-prone PCR mutagenesis; yeast genetics; transport assays (CPY, invertase); intragenic complementation |
Molecular biology of the cell |
Medium |
11160834
|
| 2002 |
Activated Arf1-GTP recruits coatomer to Golgi membranes; once membrane-associated, coatomer has a longer residence time than Arf1 and persists after Arf1-GTP hydrolysis and dissociation; Arf1 and coatomer cycle rapidly and stochastically on membranes even without vesicle budding. |
FRAP of fluorescently labeled coatomer and Arf1-GFP in living cells; quantitative live-cell imaging |
Nature |
High |
12000962
|
| 2002 |
Genetic interaction screen in yeast identified that ARF1 and TRS130 (TRAPP complex component) are synthetically lethal; YPT31/32 high-copy suppresses arf1Δtrs130 lethality; these genetic interactions link Arf1 and TRAPP signaling. |
Yeast synthetic lethal screen; high-copy suppressor screen; yeast genetics |
Yeast |
Medium |
12210902
|
| 2003 |
Arf1 inactivation early in mitosis leads to dissociation of peripheral Golgi proteins and subsequent Golgi disassembly; maintaining Arf1 in the active GTP-bound state (via H89 treatment or GTP-locked expression) prevents Golgi disassembly and causes defects in chromosome segregation and cytokinetic furrow ingression. |
Live-cell imaging; GFP-Arf1 overexpression; pharmacological activation (H89); constitutively active ARF1 expression; quantitative microscopy |
Proceedings of the National Academy of Sciences of the United States of America |
High |
14585930
|
| 2003 |
ARF1 directly binds the carboxy-terminal tail domain of the 5-HT2A receptor in a GTP-enhanced manner; ARF1 plays a greater role than ARF6 in 5-HT2AR-dependent phospholipase D activation; the N376PxxY motif in the receptor is essential for ARF-dependent PLD signaling. |
GST pull-down with receptor domain fusions; co-immunoprecipitation; dominant-negative ARF constructs; in vitro GTPγS-enhanced binding |
Molecular pharmacology |
Medium |
14573774
|
| 2003 |
Pyk2 tyrosine kinase phosphorylates ASAP1 (an ARF GAP) on Tyr308 and Tyr782, inhibiting ASAP1 GAP activity toward Arf1, thereby increasing Arf1-GTP levels; Pyk2 interacts with ASAP1 via proline-rich regions of Pyk2 and the SH3 domain of ASAP1. |
Yeast two-hybrid; co-immunoprecipitation; in vitro kinase and GAP assays; fluorimetric Arf-GTPase assay; phosphopeptide mapping |
The Journal of biological chemistry |
High |
12771146
|
| 2004 |
HIV-1 Nef directly binds ARF1 and recruits it to endosomal membranes; a complex of Nef, ARF1, and βCOP can be immunoprecipitated; dominant-negative ARF1 blocks migration of Nef-CD4 complex to lysosomes, establishing ARF1 as the immediate downstream partner of Nef for CD4 lysosomal targeting. |
Direct binding assay; co-immunoprecipitation; dominant-negative ARF1; CD4 trafficking assay |
Current biology |
Medium |
15202998
|
| 2004 |
ARF1 (GDP-bound form) directly interacts with adipocyte differentiation-related protein (ADRP) on lipid droplets; GDP-ARF1 induces dissociation of ADRP from lipid droplet surfaces; BFA treatment or dominant-negative ARF1 causes ADRP dissociation. |
Yeast two-hybrid; GST pull-down; co-immunoprecipitation; BFA treatment; dominant-negative ARF1 overexpression |
Biochemical and biophysical research communications |
Medium |
15336557
|
| 2005 |
Arf1 activation mediates the recruitment of actin, cortactin, and dynamin-2 (Dyn2) to Golgi membranes; disruption of the cortactin-Dyn2 interaction reduces Dyn2 at the Golgi and blocks trans-Golgi network protein transport, establishing Arf1 as an upstream activator of an actin-cortactin-Dyn2 complex essential for post-Golgi transport. |
In vitro Golgi membrane assay; intact-cell experiments; co-immunoprecipitation; dominant-negative disruption of cortactin-Dyn2 interaction; fluorescence microscopy |
Nature cell biology |
High |
15821732
|
| 2005 |
Mislocalization or siRNA knockdown of ASAP1 (an ARF GAP) inhibits cell spreading and migration and increases GTP loading on Arf1, demonstrating that dynamic Arf1 GTP/GDP cycling (not just a single GTP state) is required for paxillin localization to focal adhesions. |
siRNA knockdown; mitochondria-targeting mislocalization strategy; GTP-loading assay; cell spreading and migration assays |
The Journal of biological chemistry |
Medium |
15632162
|
| 2005 |
Mutations in the C-terminal helix of Arf1 (position 167) reveal a novel interaction interface between Arf1-GTP and coatomer via the delta-COP longin domain, in addition to previously described interactions via switch I with beta- and gamma-COP trunk domains. |
Site-directed photolabeling; site-directed mutagenesis; in vitro binding assay |
Traffic |
Medium |
17451557
|
| 2006 |
ARF1 is activated during FcγR-mediated phagocytosis via BFA-insensitive GEFs; blocking ARF1 cycling inhibits phagosome closure; ARF1 activation is spatially and temporally downstream of ARF6 activation and depends on PI 3-kinase signaling during phagocytosis. |
FRET stoichiometric microscopy with CFP/YFP-ARF chimeras; PI 3-kinase inhibition; dominant-negative ARF1; macrophage phagocytosis assay |
PLoS biology |
High |
16669702
|
| 2007 |
Crystal structure of GTP-bound ARF1 in complex with the Arf-binding domain (ArfBD) of ARHGAP21 at 2.1 Å reveals that ARF1 interacts with both a PH domain and an adjoining C-terminal α-helix through its switch regions; site-directed mutagenesis confirmed both structural elements are required for ARF1 binding and Golgi recruitment of ARHGAP21. |
X-ray crystallography; site-directed mutagenesis; Golgi recruitment assay |
The EMBO journal |
High |
17347647
|
| 2007 |
ARF1 controls AP-1 (but not AP-2) recruitment to endosomal sites during FcγR-mediated phagocytosis; AP-1 depletion increases surface TNF-α levels; ARF1-dependent AP-1 recruitment supports clathrin-independent endosomal remodeling during phagocytosis. |
siRNA knockdown of AP-1; dominant-negative ARF1; immunofluorescence; TNF-α surface level assay |
Molecular biology of the cell |
Medium |
17914058
|
| 2007 |
Activated ARF1 drives actin polymerization on liposomes via a CDC42/N-WASP/Arp2/3 cascade, generating actin comet tails that produce movement of ARF1-carrying vesicles, demonstrating that ARF1 can generate mechanical forces via actin polymerization to contribute to vesicle fission. |
Biomimetic liposome assay with cell extracts; dominant-negative CDC42; N-WASP inhibition; live-cell actin imaging |
Proceedings of the National Academy of Sciences of the United States of America |
High |
17942688
|
| 2008 |
Arf1-GTP induces positive membrane curvature and can dimerize in a GTP-dependent manner; an Arf1 dimerization-defective mutant cannot mediate COPI vesicle formation from Golgi membranes and is lethal in yeast, despite retaining coat receptor function, establishing that GTP-induced Arf1 dimerization drives membrane curvature required for vesicle formation. |
In vitro membrane curvature assay; Arf1 dimerization-defective mutant; COPI vesicle budding assay from Golgi membranes; yeast viability assay |
Proceedings of the National Academy of Sciences of the United States of America |
High |
18689681
|
| 2008 |
GBF1-mediated ARF1 activation is required for efficient mouse hepatitis coronavirus (MHV) RNA replication; siRNA knockdown of GBF1 or ARF1, or dominant-negative ARF1, significantly inhibits MHV infection; ARF1 inactivation does not block replication complex formation per se but reduces their number. |
Dominant-negative ARF1 expression; siRNA knockdown of GBF1, BIG1, BIG2, ARF1; BFA treatment; immunofluorescence; quantitative electron microscopy |
PLoS pathogens |
High |
18551169
|
| 2009 |
Solution NMR structure of myristoylated ARF1 shows that myristoylation contributes to regulation of guanine nucleotide exchange and stable membrane association; ARF1-GTP has greater membrane affinity than ARF1-GDP, with the myristoyl group influencing both. |
Solution NMR; lipid bilayer binding assay |
Structure |
High |
19141284
|
| 2009 |
ArfGAP1 ALPS motifs bind preferentially to positively curved membranes (threshold ~35 nm radius); when Arf1-GTP and ArfGAP1 coexist on membrane tubes, ArfGAP1 generates a smooth Arf1-GTP gradient along the tube, allowing Arf1-GTP to diffuse from flat regions to compensate for localized GTP hydrolysis at curved regions. |
Giant vesicle tube-pulling assay with molecular motors/optical tweezers; quantitative fluorescence microscopy; reconstituted Arf1-GTP/ArfGAP1 system |
The EMBO journal |
High |
19927117
|
| 2010 |
Arf1 GTPase coordinates TGN association of clathrin-AP-1 coats with CYFIP/Sra/PIR121-containing complexes; Rac1/β-PIX downstream of Arf1 activates N-WASP/Arp2/3-dependent actin polymerization toward membranes, promoting tubule formation; this was recapitulated on synthetic membranes. |
Co-immunoprecipitation; reconstitution on synthetic membranes; siRNA knockdown; live-cell imaging; dominant-negative mutants |
Nature cell biology |
High |
20228810
|
| 2011 |
ARF1 directly interacts with GBF1 (the Arf1 exchange factor GEF); GBF1 and ATGL interact directly through multiple contact sites, with GBF1 HDS1/HDS2 domains localizing to lipid droplets when expressed alone; GBF1/Arf1/COPI pathway is required for delivery of the lipase ATGL to lipid droplets. |
Yeast two-hybrid; co-immunoprecipitation; direct protein binding assay; subcellular localization of domain fragments |
PloS one |
Medium |
21789191
|
| 2011 |
GDP-bound ARF1 directly interacts with the retinoblastoma protein (pRB) but not other pRB family members; in ARF1-depleted or dominant-negative ARF1-expressing cells, GDP-ARF1 is enriched on chromatin and stabilizes the pRB/E2F1 interaction, preventing E2F target gene expression and arresting cell proliferation. |
Co-immunoprecipitation; chromatin fractionation; dominant-negative ARF1; siRNA knockdown; ChIP; gene expression analysis |
Oncogene |
Medium |
21478909
|
| 2012 |
Crystal/structural analysis combined with biochemical studies shows that Arf1-GTP binds the γζ-COP subcomplex of coatomer at one site, and a second Arf1-GTP molecule binds βδ-COP at a site common to both γ- and β-COP subunits; this bivalent GTP-dependent binding mode underlies coatomer recruitment to the Golgi. |
X-ray crystallography; structure-guided mutagenesis; biochemical binding assays |
Cell |
High |
22304919
|
| 2012 |
Arl1 is necessary for Golgi recruitment of BIG1 and BIG2 (trans-Golgi-specific ARF1 GEFs) but not GBF1; Arl1 binds directly to Sec71 (Drosophila BIG1/BIG2 ortholog) via an N-terminal region, thereby directing active Arf1 preferentially to the trans-Golgi. |
Liposome-based affinity purification; direct binding assay; siRNA knockdown of Arl1; immunofluorescence |
The Journal of cell biology |
High |
22291037
|
| 2012 |
Simultaneous depletion of ARF1 and ARF3 induces tubulation of recycling endosomes and suppresses transferrin recycling from endosomes to the plasma membrane, without affecting retrograde transport from endosomes to the TGN. |
siRNA double knockdown; fluorescence microscopy; transferrin recycling assay; retrograde transport assay |
Cell structure and function |
Medium |
22971977
|
| 2013 |
ARF1 acts upstream of RhoA/RhoC to control myosin light chain (MLC) phosphorylation, invadopodia maturation, microvesicle shedding, and MMP-9 activity in invasive breast cancer cells; ARF1 depletion impairs extracellular matrix degradation and cell invasiveness. |
siRNA knockdown; dominant-negative and constitutively active ARF1; RhoA/RhoC activity assay; MLC phosphorylation assay; invadopodia and matrix degradation assay |
Molecular biology of the cell |
Medium |
24196838
|
| 2013 |
ARF1-GTP binds PICK1, limiting PICK1-mediated inhibition of Arp2/3 actin polymerization; NMDAR stimulation downregulates Arf1 activation via the Arf-GAP GIT1, releasing PICK1 to inhibit Arp2/3, thereby mediating AMPAR internalization and LTD. |
Co-immunoprecipitation; dominant-negative Arf1 that does not bind PICK1; FRET-based GTPase assay; organotypic slice LTD recordings; spine morphology analysis |
Neuron |
High |
23889934
|
| 2013 |
ARF1 controls Rac1 activation downstream of EGF; ARF1 and Rac1 directly interact regardless of nucleotide state; ARF1 is required for plasma membrane targeting of Rac1 and IRSp53 for lamellipodia formation and cell migration in invasive breast cancer cells. |
siRNA knockdown; direct interaction assay; dominant-negative Rac1 rescue; GTP-loading assay; plasma membrane fractionation |
Cellular signalling |
Medium |
23707487
|
| 2013 |
Simultaneous depletion of ARF1 and ARF4 induces tubulation of recycling endosomes and inhibits retrograde transport of TGN38 and mannose-6-phosphate receptor from early/recycling endosomes to the TGN, a pathway distinct from ARF1+ARF3-dependent transferrin recycling. |
siRNA double knockdown; immunofluorescence; transferrin and TGN38 trafficking assays |
Molecular biology of the cell |
Medium |
23783033
|
| 2014 |
Arf1/COPI proteins localize to cellular lipid droplets (LDs), bud nano-LDs (~60 nm) from LD surfaces, and are required for targeting specific TG-synthesis enzymes to LD surfaces; loss of Arf1/COPI function increases LD phospholipid content, decreasing surface tension and impairing LD-ER bridge formation. |
Live-cell imaging; super-resolution microscopy; in vitro nano-LD budding assay; phospholipid quantification; ER-LD contact site analysis |
eLife |
High |
24497546
|
| 2014 |
ARF1 regulates adhesion of invasive breast cancer cells by controlling recruitment of paxillin, talin, and FAK to β1-integrin at focal adhesions; ARF1 can be found in complex with β1-integrin, paxillin, talin, and FAK; ARF1 is essential for EGF-mediated FAK and Src phosphorylation. |
siRNA knockdown; co-immunoprecipitation; immunofluorescence; focal adhesion assay; phosphorylation assays |
Cellular signalling |
Medium |
25530216
|
| 2014 |
Adaptor protein Grb2 promotes ARF1 activation and recruits ARF1 to EGFR; p66Shc blocks ARF1 activation and receptor recruitment by preventing Grb2/ARF1 complex formation; ARF1 can be co-immunoprecipitated with both Grb2 and p66Shc upon EGF stimulation. |
Co-immunoprecipitation; siRNA knockdown; ARF1 activation assay; receptor recruitment assay |
The Journal of biological chemistry |
Medium |
24407288
|
| 2014 |
NMR-based structural data shows that yeast Arf1 interacts with the PH domain of Fapp1 at a membrane surface through contacts between switch I of Arf1 and regions near the C-terminal extension of the Fapp1 PH domain, with the Arf1-binding site distinct from the PI4P-binding site, supporting coincidence detection of active ARF1 and PI4P for Fapp1 membrane recruitment. |
Solution NMR with membrane-surface interaction mapping |
Structure |
High |
24462251
|
| 2014 |
In yeast, Arf1 interacts with the vacuolar ATPase (V-ATPase) and is required for glucose-induced Ras/PKA activation; cytosolic pH acts as a signal linking glucose availability to Ras/PKA through the V-ATPase–Arf1 axis. |
Genetic epistasis; co-immunoprecipitation; in vivo pH measurement; Ras/PKA activity assays |
Molecular cell |
Medium |
25002144
|
| 2014 |
ARF1-GTP regulates Asrij endocytic function in Drosophila blood cells; ARF1-GTP is essential for hematopoietic niche size and prohemocyte maintenance; ARF1 perturbation causes aberrant Notch trafficking and stalls the Notch intracellular domain in sorting endosomes. |
RNA interference in Drosophila lymph gland; GEF knockdown (Gartenzwerg); GAP overexpression; Notch trafficking assay by immunofluorescence; co-immunoprecipitation |
Proceedings of the National Academy of Sciences of the United States of America |
Medium |
24707047
|
| 2014 |
E. coli EspG scaffolds tether vesicles through selective ARF1-GTP/effector complexes while locally inactivating Rab1, inducing bidirectional ER-Golgi traffic arrest; structural modeling reveals that EspG binds ARF1-GTP specifically. |
Structural modeling; co-immunoprecipitation; dominant-negative studies; cell-based trafficking assay |
Cell reports |
Medium |
24582959
|
| 2015 |
HIV-1 Nef and Arf1 together induce trimerization and allosteric activation of AP-1; cryo-EM structures of the Nef- and Arf1-bound AP-1 trimer reveal a central nucleus of three Arf1 molecules organizing the trimers; reconstitution of clathrin cage assembly validated a predicted hexagonal AP-1 coat assembly. |
Cryo-electron microscopy; in vitro clathrin cage reconstitution; structural validation of hexagonal assembly model |
Science |
High |
26494761
|
| 2015 |
GIV/Girdin activates Gαi at the Golgi, which interacts with active Arf1, ArfGAP2/3, and β-COP to impose finiteness on Arf1 GTPase cycling; inhibition of the GIV-Gαi pathway elevates GTP-bound Arf1 and delays protein transport along the secretory pathway. |
Co-immunoprecipitation; GIV-GEF inhibition; ARF1-GTP loading assay; protein transport assay |
Developmental cell |
Medium |
25865347
|
| 2016 |
Podosome assembly requires the GTPase ARF1 and its GEF ARNO; ARF1 inhibition increases RhoA-GTP levels and triggers myosin-IIA filament assembly, causing podosome elimination; myosin-IIA suppression rescues podosome formation despite ARF1 inhibition; constitutively active ARF1 induces podosome precursor (actin-rich puncta) formation. |
siRNA knockdown of ARF1 and ARNO; pharmacological inhibitors; constitutively active ARF1 expression; RhoA-GTP assay; myosin-IIA rescue experiment |
The Journal of cell biology |
High |
28007915
|
| 2016 |
ARF1-mediated MAPK signaling (ERK1/2) in prostate cancer requires Thr48 in ARF1; mutation of Thr48 abolishes ARF1's ability to activate ERK1/2 and promote cell proliferation; ARF1 activity correlates with ERK1/2 phosphorylation and tumor growth in xenograft models. |
ARF1 overexpression and knockdown; T48 point mutant; Raf1/MEK inhibitors; xenograft mouse model; ERK1/2 phosphorylation assay |
Oncotarget |
Medium |
27213581
|
| 2017 |
ARF1-GTP is functionally required for formation of long thin (~3 µm, ~110 nm diameter) tubular carriers from the Golgi that carry anterograde and retrograde cargo; these tubules are largely free of COPI and clathrin coat proteins, representing a COPI-independent ARF1 function. |
CRISPR/Cas9-edited ARF1; super-resolution nanoscopy (STED); dynamic confocal imaging; ARF1 GTP-hydrolysis mutant |
Molecular biology of the cell |
High |
28428254
|
| 2018 |
BIG1/Arfgef1 and Arf1 regulate initiation of myelination by Schwann cells; Schwann cell-specific BIG1 knockout reduces myelin thickness and myelin protein zero membrane localization; BIG1 knockout decreases Arf1 binding to AP-1 clathrin adaptor subunits specifically, without affecting Arf1 binding to GGA1 or COPI. |
Conditional knockout mice (Schwann cell-specific BIG1 KO; Arf1 conditional KO); electron microscopy of myelin; co-immunoprecipitation of Arf1 with coat complexes |
Science advances |
High |
29740613
|
| 2018 |
BIG2-ARF1 activates RhoA, which through mDia1 promotes Golgi deployment into major dendrites; BIG2 and ARF1 co-localize with the Golgi apparatus in hippocampal neurons; constitutively active ARF1(Q71L) rescues dendrite morphogenesis defects in BIG2-null neurons. |
siRNA knockdown; constitutively active ARF1 rescue; RhoA activation assay; immunofluorescence; in utero electroporation |
Molecular neurobiology |
Medium |
29455446
|
| 2018 |
GBF1 and active Arf1-GTP interact with Miro (a mitochondrial membrane protein); inhibition of GBF1 or Arf1 activation promotes dynein- and Miro-dependent retrograde mitochondrial transport towards the centrosome; GBF1 inhibition results in a two-fold increase in retrograde mitochondrial movement. |
Co-immunoprecipitation of GBF1 and Arf1-GTP with Miro; live-cell mitochondrial tracking; GBF1 inhibition; Miro siRNA; dynein inhibitor |
Scientific reports |
Medium |
30459446
|
| 2018 |
Cell-matrix adhesion controls Arf1 activation; loss of adhesion reduces active Arf1-GTP and disorganizes the Golgi along microtubules; constitutively active Arf1 prevents adhesion-dependent Golgi disorganization; adhesion-dependent Arf1 activation regulates Arf1 binding to dynein to control Golgi positioning and cell surface glycosylation. |
Co-immunoprecipitation (Arf1-dynein); constitutively active Arf1; integrin-blocking antibody; Arf1-GTP loading assay; surface glycosylation assay |
Journal of cell science |
Medium |
30054383
|
| 2020 |
Arf1 ablation in cancer cells induces mitochondrial defects and ER stress, causing release of damage-associated molecular patterns (DAMPs) that recruit and activate dendritic cells; this triggers CD8+ T cell infiltration and activation, establishing Arf1-mediated lipid metabolism as a regulator of tumor immune surveillance. |
Arf1 genetic ablation; mitochondrial function assay; DAMP release assay; DC recruitment assay; T cell activation assay; mouse tumor models |
Nature communications |
Medium |
31924786
|
| 2020 |
Low phosphatidylcholine (PC) synthesis or LPIN1 knockdown in mammalian cells reduces GTP-bound ARF1 levels, linking changes in lipid ratios (PC content) to ARF1 inactivation and consequent SREBP-1 maturation. |
RNAi screen in C. elegans; siRNA knockdown in mammalian cells; ARF1-GTP loading assay |
Cell reports |
Medium |
27320911
|
| 2021 |
Arf1 directly recruits the Pik1-Frq1 PI4-kinase complex to the Golgi in yeast; this Arf1-dependent PI4P production is a critical upstream signal for AP-1 recruitment and secretory vesicle formation at maturing Golgi compartments. |
In vitro protein-protein interaction assay on Golgi-mimetic membranes; acute PI4P depletion; live-cell time-lapse imaging |
Molecular biology of the cell |
High |
33788598
|
| 2021 |
Arf1 recruits Gyp1 (Rab-GAP) to the TGN to drive Ypt1 (Rab1) inactivation, thereby orchestrating Rab GTPase conversion on maturing Golgi compartments; Arf1 is a master regulator of Rab conversion through this GAP-recruitment mechanism. |
Yeast genetic analysis; live-cell imaging of Rab conversion; epistasis analysis with Arf1 and TRAPPII mutants |
Molecular biology of the cell |
Medium |
33788577
|
| 2021 |
ARF1 interacts with IQGAP1 and promotes colon tumorigenesis via activation of ERK signaling and mitochondrial fission through enhanced IQGAP1-MEK-ERK interaction and increased Drp1 phosphorylation; the drug azelastine binds Thr-48 of ARF1 and inhibits this pathway. |
Co-immunoprecipitation; DARTS target identification; Biacore binding assay; ARF1-T48S mutant; cell proliferation and xenograft assays |
Theranostics |
Medium |
33408784
|
| 2022 |
CryoEM structures of full-length Gea2 (yeast GBF1 ortholog) reveal organization of regulatory domains and how the GEF domain adopts two conformations corresponding to different stages of the Arf1 activation reaction; a Gea2-Arf1 activation intermediate structure suggests GEF domain movement primes Arf1 for membrane insertion upon GTP binding. |
CryoEM of full-length Gea2; structural analysis of Gea2-Arf1 intermediate |
Cell reports |
High |
36044848
|
| 2023 |
Heterozygous GTPase-defective ARF1 missense mutations cause type I interferonopathy; mutated ARF1 perturbs mitochondrial morphology causing aberrant mitochondrial DNA release and cGAS activation, and also causes accumulation of active STING at the Golgi/ERGIC due to defective retrograde STING transport; ARF1 thus has a dual role in maintaining cGAS-STING homeostasis. |
Patient-derived cell lines with ARF1 missense mutations; IFN-stimulated gene expression assay; mitochondrial morphology analysis; STING trafficking assay; cell line overexpression of disease mutants |
Nature communications |
High |
37914730
|
| 2023 |
A hyperactive Arf1 mutant in yeast decreases expression of fatty acid transporters and the rate-limiting β-oxidation enzyme, causing fatty acid accumulation in lipid droplets and mitochondrial fragmentation with reduced ATP synthesis; genetic/pharmacological depletion of fatty acids phenocopies the Arf1 mutant mitochondrial phenotype, linking Arf1 to fatty acid storage/utilization balance. |
Yeast hyperactive Arf1 mutant; transcriptomics; lipid droplet staining; mitochondrial morphology; ATP measurement; fatty acid depletion |
Nature cell biology |
High |
37400497
|
| 2024 |
ARF1 compartments (tubulo-vesicular structures harboring clathrin and different AP complexes) comprise two functional classes: perinuclear ARF1 compartments facilitate Golgi export of secretory cargo, while peripheral ARF1 compartments mediate endocytic recycling downstream of early endosomes; ARF1 compartments mature into recycling endosomes, and this maturation requires AP-1. |
CRISPR-Cas9 endogenous tagging; fast confocal live-cell imaging; STED super-resolution microscopy; correlative light and electron microscopy; AP-1 depletion |
Nature cell biology |
High |
39367144
|
| 2024 |
Astrocytic LRP1 suppresses lactate production and thereby reduces ARF1 lactylation; elevated ARF1 lactylation (a post-translational modification) in LRP1-depleted astrocytes impairs mitochondria transfer from astrocytes to neurons. |
LRP1 knockdown in astrocytes; ARF1 lactylation detection; mitochondria transfer assay; mouse ischemia-reperfusion model |
Cell metabolism |
Medium |
38906140
|