Affinage

ARFGAP1

ADP-ribosylation factor GTPase-activating protein 1 · UniProt Q8N6T3

Length
406 aa
Mass
44.7 kDa
Annotated
2026-04-28
41 papers in source corpus 30 papers cited in narrative 30 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARFGAP1 is a curvature-sensing GTPase-activating protein central to vesicular trafficking, coat dynamics, and signaling at endomembranes. It catalyzes GTP hydrolysis on Arf1 (and Arl1) through an N-terminal zinc-finger GAP domain and is targeted to curved Golgi and vesicular membranes by two amphipathic lipid-packing sensor (ALPS) motifs that fold into helices selectively on highly curved bilayers, coupling COPI coat disassembly kinetics to membrane geometry (PMID:14654841, PMID:15944734, PMID:17253781). Beyond COPI-dependent transport, ARFGAP1 functions as a stoichiometric coat component that directly binds dilysine cargo motifs and coatomer to promote cargo sorting and vesicle budding, interacts with AP-1 and AP-2 clathrin adaptors through its C-terminal WETF motif to regulate endocytosis independently of COPI function, and acts as a GAP for Arl1 at the TGN to support endosome-to-TGN retrograde traffic (PMID:12379802, PMID:21499258, PMID:33715220). ARFGAP1 also operates outside canonical vesicle trafficking: it serves as a GAP and phosphorylation substrate for the Parkinson's disease kinase LRRK2—where reducing ARFGAP1 activity rescues LRRK2-G2019S neurotoxicity—and it inhibits mTORC1 lysosomal activation via ALPS-motif-dependent interaction and regulates cortical actin reorganization through antagonism of Rac1 (PMID:22363216, PMID:22423108, PMID:33988249, PMID:21483700).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 2001 High

    Demonstrating that cargo proteins actively regulate ArfGAP1 established that GAP activity during COPI vesicle formation is not constitutive but is tuned by transmembrane cargo, providing the first evidence for a cargo-based coat regulation mechanism.

    Evidence Synthetic peptide inhibition of ArfGAP1 GTP hydrolysis on Arf1-loaded liposomes and Golgi membranes by the p24beta1 cytoplasmic domain

    PMID:11748249

    Open questions at the time
    • Stoichiometry and affinity of p24-ArfGAP1 complexes on native Golgi not determined
    • Whether other p24 family members exert similar regulation was untested
  2. 2002 High

    Reconstituting COPI vesicle formation revealed that ARFGAP1 is not merely a terminator of Arf1 signaling but a stoichiometric coat component that directly contacts dilysine cargo, redefining the role of GAPs in vesicle biogenesis.

    Evidence Reconstitution of COPI vesicle budding from Golgi membranes with purified components and direct cargo-binding assays

    PMID:12379802

    Open questions at the time
    • Structural basis of ARFGAP1-cargo interaction not resolved
    • Relative contributions of ARFGAP1 vs. coatomer in cargo selection unclear
  3. 2003 High

    Showing that ArfGAP1 catalytic activity increases over two orders of magnitude with increasing membrane curvature established the principle that coat disassembly is physically coupled to vesicle geometry, a new paradigm for self-regulating coat cycles.

    Evidence Time-resolved COPI dynamics assays on liposomes of controlled diameter

    PMID:14654841

    Open questions at the time
    • Molecular mechanism of curvature sensing was unknown at this point
    • Relevance to in vivo curvature range not yet tested
  4. 2005 High

    Identification and biophysical characterization of the ALPS motif explained the curvature-sensing mechanism: an intrinsically disordered segment that folds into an amphipathic helix on loosely packed (curved) membranes, directly linking lipid packing defects to GAP recruitment and activity.

    Evidence Site-directed mutagenesis, circular dichroism, limited proteolysis, and liposome binding assays

    PMID:15944734 PMID:16316994

    Open questions at the time
    • Atomic-resolution structure of ALPS on a curved membrane was lacking
    • Contribution of a potential second ALPS motif was not yet appreciated
  5. 2005 High

    Biochemical reconstitution demonstrated that ArfGAP1 GAP catalytic activity is required for COPI vesicle formation and that ArfGAP1—not Arf1-GTP—directly promotes coatomer engagement with cargo, separating GAP and coat-assembly functions.

    Evidence COPI vesicle formation assays with catalytic mutants and purified components

    PMID:15657398

    Open questions at the time
    • Whether GAP-dead ArfGAP1 can still sort cargo in vivo was unclear
    • Temporal ordering of GAP activity relative to coat polymerization not resolved
  6. 2005 High

    Live-cell FRAP showed that ArfGAP1 Golgi dynamics depend on coatomer and Arf1 engagement, validating the in vitro coat-cycle model in living cells and showing ~40% of ArfGAP1 membrane exchange is coat-dependent.

    Evidence FRAP of GFP-ArfGAP1 in cells expressing dominant-active Arf1 or depleted of coatomer

    PMID:15795316

    Open questions at the time
    • Remaining ~60% of membrane exchange mechanism was uncharacterized
    • Role of lipid composition in vivo Golgi binding not assessed
  7. 2005 High

    ArfGAP1-induced Arf1 GTP hydrolysis triggers AP-1 complex disassembly from membranes, and AP-1 itself stimulates ArfGAP1 activity, demonstrating a reciprocal regulatory loop between adaptor complexes and GAP function beyond COPI.

    Evidence In vitro reconstitution with purified AP-1, Arf1, ArfGAP1, and synthetic liposomes

    PMID:16093346

    Open questions at the time
    • In vivo relevance for AP-1-dependent TGN-to-endosome trafficking not directly tested
    • Whether this mechanism operates at specific subdomains of the TGN unknown
  8. 2007 High

    Discovery of a second ALPS motif (ALPS2) that reinforces membrane binding ~40-fold expanded the curvature-response range of ArfGAP1, explaining how it can operate across diverse organelle geometries.

    Evidence Quantitative liposome binding, circular dichroism, and Golgi localization of ALPS mutants

    PMID:17253781

    Open questions at the time
    • Whether ALPS1 and ALPS2 insert simultaneously or sequentially was unknown
    • Functional contribution of ALPS2 to GAP catalysis in vivo not tested
  9. 2008 High

    Comparison with ArfGAP2/3 showed that ArfGAP1 is unique among Golgi ArfGAPs in binding membranes independently of coatomer, establishing that curvature sensing and coatomer dependence define two parallel GAP recruitment strategies at the Golgi.

    Evidence In vitro membrane binding and GTPase assays comparing ArfGAP1, ArfGAP2, and ArfGAP3 with and without coatomer

    PMID:19015319

    Open questions at the time
    • Functional redundancy vs. specificity among Golgi ArfGAPs in vivo not fully delineated
  10. 2009 High

    Reconstitution on membrane nanotubes demonstrated that ArfGAP1 reads curvature with a threshold radius of ~35 nm and creates smooth Arf1-GTP gradients along curved membranes, establishing a quantitative biophysical framework for curvature-coupled coat dynamics.

    Evidence Nanotube pulling from giant vesicles with optical tweezers and fluorescence imaging

    PMID:19927117

    Open questions at the time
    • Whether native Golgi tubule curvature reaches the 35-nm threshold was not confirmed
    • Effects of lipid heterogeneity on curvature threshold not explored
  11. 2010 Medium

    Mapping of C-terminal coat-interaction motifs revealed that ARFGAP1 uses a WETF sequence for AP-1/AP-2 binding and a distinct C-terminal tryptophan-containing motif for coatomer delta-subunit binding, providing the molecular basis for its dual coat engagement.

    Evidence GST pulldown with peptides, mutagenesis, and in vivo reporter assays

    PMID:20211604

    Open questions at the time
    • Crystal structure of ARFGAP1 C-terminus with AP-2 or coatomer not available
    • Quantitative binding parameters not determined
  12. 2011 High

    Selective disruption of AP-2 versus coatomer interaction domains showed that ARFGAP1 participates in AP-2-mediated endocytosis as a bona fide clathrin coat component, independent of its COPI function—expanding its role beyond the Golgi.

    Evidence Domain-selective mutants assessed in separate COPI and AP-2 transport pathway assays

    PMID:21499258

    Open questions at the time
    • Cargo specificity of ARFGAP1 in AP-2-dependent endocytosis not defined
    • Whether ARFGAP1 GAP activity at the plasma membrane uses ARF6 or ARF1 as substrate was not resolved here
  13. 2011 Medium

    The non-catalytic C-terminal domain of ARFGAP1 was found to antagonize Rac1 activation and inhibit actin cytoskeleton reorganization and cell spreading, revealing a GAP-independent signaling function.

    Evidence Overexpression of C-terminal truncation mutants with live imaging and Rac1 activation assays

    PMID:21483700

    Open questions at the time
    • Direct binding between ARFGAP1 C-terminus and Rac1 or a Rac1 GEF/GAP not demonstrated
    • Physiological context for this Rac1 regulation unknown
  14. 2012 High

    Two independent studies established that ARFGAP1 acts as a GAP for the Parkinson's-associated kinase LRRK2 and is reciprocally phosphorylated by it; reducing ARFGAP1 function rescues LRRK2-G2019S neurotoxicity, linking ARFGAP1 to neurodegeneration pathways.

    Evidence In vitro GTPase/kinase assays, reciprocal Co-IP, siRNA/shRNA knockdown with neurite morphology and Drosophila toxicity readouts across two labs

    PMID:22363216 PMID:22423108

    Open questions at the time
    • In vivo phosphorylation sites on ARFGAP1 by LRRK2 were not mapped at this time
    • Whether GAP activity toward LRRK2 and Arf1 is structurally separable was unclear
  15. 2014 Medium

    ARFGAP1 was co-opted by HCV NS5A to exclude the PI4P phosphatase Sac1 from viral replication sites, maintaining elevated PI4P levels needed for viral replication—demonstrating pathogen exploitation of ARFGAP1 cargo-sorting function.

    Evidence Co-immunoprecipitation, NS5A mutagenesis, PI4P quantification, and ARFGAP1 knockdown in HCV-replicating cells

    PMID:24623438

    Open questions at the time
    • Whether ARFGAP1 GAP activity or only its coat function is required for HCV was not resolved
    • Generality to other Flaviviridae not tested
  16. 2014 Medium

    PLD2-generated phosphatidic acid was shown to be required for ARFGAP1 Golgi recruitment, identifying a specific lipid signal upstream of ALPS-mediated binding.

    Evidence PLD2 inhibitors and siRNA with ArfGAP1 localization readout

    PMID:25354038

    Open questions at the time
    • Whether PA acts through ALPS motifs or a distinct binding site was not determined
    • Relationship between PA and membrane curvature sensing not clarified
  17. 2017 Medium

    Silencing ARFGAP1 in the Arf1-PLD1 cortical actin pathway led to uncontrolled uptake and intracellular replication of Mycobacterium tuberculosis, establishing ARFGAP1 as a regulator of host defense through actin cytoskeleton control.

    Evidence siRNA knockdown, actin imaging, Mycobacterium infection assay, epistasis with Arf1/PLD1

    PMID:29141986

    Open questions at the time
    • Whether ARFGAP1 actin regulation in infection operates through Rac1 antagonism was not tested
    • Relevance to macrophage infection unclear
  18. 2021 High

    ARFGAP1 was identified as a GAP for Arl1 at the TGN, broadening its substrate repertoire beyond Arf1 and connecting it to endosome-to-TGN retrograde transport of Shiga toxin.

    Evidence In vitro GTPase assay, TGN displacement by overexpression of wild-type vs. catalytically dead mutant, siRNA knockdown with Shiga toxin trafficking readout

    PMID:33715220

    Open questions at the time
    • Structural basis for Arl1 recognition by the ARFGAP1 zinc-finger domain not determined
    • Whether Arl1 GAP activity is curvature-dependent like Arf1 GAP activity is unknown
  19. 2021 Medium

    ARFGAP1 was shown to interact with mTORC1 via its ALPS motifs under amino acid starvation and to inhibit mTORC1 lysosomal localization and activation, revealing a nutrient-sensing signaling role independent of vesicle coat function.

    Evidence Co-immunoprecipitation, ALPS mutagenesis, mTORC1 activity assays, lysosomal fractionation

    PMID:33988249

    Open questions at the time
    • Whether ARFGAP1 senses lysosomal membrane curvature to regulate mTORC1 is speculative
    • Mechanism by which ALPS-mTORC1 interaction prevents lysosomal recruitment not defined
  20. 2023 Medium

    Drosophila genetic studies showed ArfGAP1 maintains receptor tyrosine kinases at the plasma membrane by regulating endosomal sorting, with genetic epistasis placing ArfGAP1 upstream of Lrrk in this pathway—connecting its trafficking and LRRK2-regulatory roles in vivo.

    Evidence Loss-of-function genetics in border cells, receptor localization imaging, endosome morphometry, genetic epistasis with Lrrk

    PMID:37599820

    Open questions at the time
    • Whether the mammalian ARFGAP1-LRRK2 axis regulates RTK sorting similarly is untested
    • Mechanism of ArfGAP1 action in endosomal sorting (GAP activity vs. scaffolding) not dissected

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of ALPS motif curvature sensing at atomic resolution on native membranes, whether ARFGAP1's GAP activity toward distinct substrates (Arf1, Arl1, LRRK2) is structurally and spatially separable, and how LRRK2 phosphorylation of the ALPS2 motif integrates with curvature sensing to control ARFGAP1 localization and function in neurodegeneration.
  • Atomic structure of ALPS on curved membrane unavailable
  • In vivo substrate selectivity among Arf1, Arl1, ARF6, and LRRK2 not resolved
  • Physiological consequences of LRRK2-mediated phosphorylation of ALPS2 in mammalian brain tissue not confirmed in peer-reviewed studies

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 8 GO:0003924 GTPase activity 7 GO:0008289 lipid binding 5 GO:0060090 molecular adaptor activity 3
Localization
GO:0005794 Golgi apparatus 6 GO:0031410 cytoplasmic vesicle 3 GO:0005829 cytosol 2 GO:0005811 lipid droplet 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 7 R-HSA-9609507 Protein localization 5 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 1
Partners
AP1B1AP2A1ARF1ARL1COPALRRK2TMED2
Complex memberships
AP-2 clathrin coatCOPI coat

Evidence

Reading pass · 30 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2003 ArfGAP1-catalysed GTP hydrolysis in Arf1 and COPI coat disassembly increase over two orders of magnitude as membrane bilayer curvature increases, coupling COPI coat disassembly to membrane curvature through lipid packing sensing. Time-resolved in vitro assays for COPI dynamics on liposomes of controlled size Nature High 14654841
2005 A central ~40-amino acid ALPS (ArfGAP1 Lipid Packing Sensor) motif in ArfGAP1 is unstructured in solution but folds into an amphipathic helix on highly curved membranes by inserting bulky hydrophobic residues between loosely packed lipids, coupling ArfGAP1 activity to membrane curvature. Site-directed mutagenesis, limited proteolysis, circular dichroism, liposome binding assays The EMBO journal High 15944734
2002 ARFGAP1 promotes COPI vesicle formation and cargo sorting by functioning as a stoichiometric component of the COPI coat; it binds directly to the dilysine motif of cargo proteins. Reconstitution of COPI vesicle formation from Golgi membranes with purified components; cargo binding assays The Journal of cell biology High 12379802
2001 The cytoplasmic domain of p24beta1 binds ArfGAP1 directly and inhibits ArfGAP1-mediated GTP hydrolysis on Arf1 bound to liposomes and Golgi membranes, suggesting cargo proteins regulate ArfGAP1 activity during COPI vesicle formation. Synthetic peptide inhibition assays, in vitro GTP hydrolysis assays on liposomes and Golgi membranes The Journal of cell biology High 11748249
2005 ArfGAP1 GAP catalytic activity plays a critical role in COPI vesicle formation from Golgi membrane, and ArfGAP1 (not ARF1) directly promotes cargo binding by coatomer. Reconstituted COPI vesicle formation assay, cargo binding experiments with purified proteins The Journal of cell biology High 15657398
2005 ArfGAP1 membrane exchange at the Golgi is ~40% dependent on engagement with coatomer and Arf1; permanent Arf1 activation traps ArfGAP1 on the Golgi in a coatomer-dependent manner, demonstrating interdependent roles of ArfGAP1, coatomer, and Arf1 in the COPI coat assembly-disassembly cycle in vivo. FRAP of GFP-tagged ArfGAP1, Arf1, and coatomer in living cells The Journal of cell biology High 15795316
2007 ArfGAP1 contains a second ALPS2 motif that also folds into an amphipathic helix on small vesicles; ALPS1 is the primary membrane-binding determinant and ALPS2 reinforces this interaction ~40-fold, enabling ArfGAP1 to respond to a wide range of membrane curvature. Quantitative liposome binding assays (fluorescence and sedimentation), circular dichroism, in vivo Golgi localization of mutants Biochemistry High 17253781
2008 ArfGAP2 and ArfGAP3 (unlike ArfGAP1) do not bind directly to membranes but require coatomer for membrane recruitment; coatomer stimulates ArfGAP2/3 GAP activity, demonstrating a coatomer-dependent mechanism distinct from ArfGAP1's curvature-sensing mechanism. In vitro membrane binding assays, GTP hydrolysis assays with and without coatomer The Journal of cell biology High 19015319
2009 ArfGAP1 binds exclusively to positively curved membrane tubes (threshold radius ~35 nm) via its ALPS motifs, generating a smooth Arf1-GTP gradient along tubes pulled from giant vesicles; catalytic amounts of ArfGAP1 drive Arf1 off curved regions, which are replenished by Arf1-GTP diffusing from flat regions. Membrane nanotube pulling from giant vesicles with molecular motors and optical tweezers; fluorescence microscopy The EMBO journal High 19927117
2005 Hydrophobic residues (Leu-207, Trp-211) within a short stretch (residues 204–214) of ArfGAP1 are critical for its Golgi localization and for in vitro GAP activity on Arf1 bound to Golgi membranes; this stretch overlaps with the ALPS motif mediating lipid-packing sensing. Alanine scanning mutagenesis, in vitro GAP activity assays on Golgi membranes, cell localization studies The Journal of biological chemistry High 16316994
2008 Golgi targeting of ArfGAP1 depends on folding into two amphipathic helices (mapped by proline replacement and alanine insertion) within residues 199–294; most hydrophobic residues in this region contribute to Golgi interaction. Point mutation, proline replacement, alanine insertion analysis with in vivo Golgi localization readout; circular dichroism for helix folding The Journal of biological chemistry Medium 18195007
2010 ArfGAP1 interacts with clathrin adaptors AP1 and AP2 through a C-terminal WETF sequence, and binds coatomer through its extreme C-terminal sequence (AADEGWDNQNW) via the delta-subunit of the coatomer adaptor-like subcomplex. GST pulldown with peptides, mutagenesis, peptide competition, reporter fusion assay in vivo Biochemical and biophysical research communications Medium 20211604
2011 Distinct regions of ARFGAP1 interact with AP-2 and coatomer separately; selective disruption of each interaction inhibits only the corresponding transport pathway (AP-2-mediated endocytosis or COPI transport), and both GAP activity and coat function of ARFGAP1 contribute to AP-2 transport. Interaction mapping, domain-selective disruption, transport pathway assays Nature cell biology High 21499258
2012 ArfGAP1 functions as a GTPase-activating protein for LRRK2, markedly enhancing LRRK2 GTP hydrolysis activity; ArfGAP1 also promotes LRRK2 kinase activity. Reciprocally, LRRK2 directly phosphorylates ArfGAP1 in vitro. ArfGAP1 and LRRK2 interact in vitro, in mammalian cells, and in vivo in brain, co-localizing at Golgi membranes. Silencing ArfGAP1 rescues G2019S LRRK2-induced neurite shortening. Co-immunoprecipitation, in vitro GTPase/kinase assays, in vitro phosphorylation, siRNA knockdown with neuronal morphology readout PLoS genetics High 22363216
2012 ArfGAP1 binds LRRK2 predominantly via the WD40 and kinase domains of LRRK2; ArfGAP1 increases LRRK2 GTPase activity and its GAP activity is inhibited by LRRK2 phosphorylation; LRRK2 autophosphorylation and kinase activity are reduced in the presence of ArfGAP1. Dominant-negative ArfGAP1 (Δ64) and shRNA knockdown reduce LRRK2 toxicity in vitro and in Drosophila. Co-immunoprecipitation, in vitro GTPase/kinase assays, domain-mapping, shRNA knockdown, Drosophila in vivo toxicity The Journal of neuroscience High 22423108
2005 ArfGAP1-induced GTP hydrolysis in Arf1 causes disassembly of AP-1 oligomeric complexes from membranes; AP-1 stimulates ArfGAP1 activity, suggesting AP-1 participates in regulating the Arf1 GTPase timer. In vitro reconstitution with purified AP-1, Arf1, ArfGAP1, and synthetic liposomes; gel filtration for complex size Molecular biology of the cell High 16093346
2008 ARFGAP1 binds directly to the C terminus of GAT1 (GABA transporter-1), and surface expression of a COPII-independent GAT1 mutant requires ARFGAP1, placing ARFGAP1 in a non-conventional ER export pathway for GAT1. Direct binding assay (pulldown), siRNA knockdown, surface expression measurement The Journal of neuroscience Medium 19020038
2011 The non-catalytic C-terminal domain of ARFGAP1 (residues sufficient in a 65-aa C-terminal fragment) antagonizes Rac1 activation downstream of serum stimulation, inhibiting actin cytoskeleton reorganization and cell spreading; constitutively active Rac1 suppresses this effect. Overexpression of truncation mutants, live cell imaging, Rac1 activation assay, epistasis with constitutively active ARF6 and Rac1 PloS one Medium 21483700
2011 ArfGAP1 promotes coatomer polymerization into spherical structures and facilitates coatomer-induced deformation of large unilamellar vesicles; ArfGAP1 overexpression in vivo induces vesicle accumulation while maintaining normal COPI cargo trafficking. In vitro coatomer polymerization assay, LUV deformation assay, electron microscopy, in vivo overexpression Cellular logistics Medium 22279613
2014 HCV NS5A interacts with ARFGAP1 (via a conserved cluster of positively charged residues in NS5A), hijacking ARFGAP1 to exclude the COPI cargo Sac1 (PI4P phosphatase) from the replication site, thereby maintaining elevated PI4P levels required for HCV replication. Co-immunoprecipitation, knockdown, PI4P measurement, mutagenesis of NS5A Journal of virology Medium 24623438
2021 ArfGAP1 interacts with mTORC1 in the absence of amino acids via its ALPS motifs and inhibits mTORC1 lysosomal localization and activation; ALPS motif mutations abrogate both ArfGAP1-mTORC1 interaction and mTORC1 inhibition. Co-immunoprecipitation, lysosomal fractionation, mTORC1 activity assays, ALPS motif mutagenesis The EMBO journal Medium 33988249
2021 ArfGAP1 acts as a GAP for human Arl1, directly interacting with GTP-bound Arl1 and stimulating its GTP hydrolysis in vitro; ArfGAP1 overexpression (but not catalytically dead mutant) displaces Arl1 from the TGN, and ArfGAP1 knockdown impairs endosome-to-TGN retrograde transport of Shiga toxin B-subunit. In vitro GTPase assay, activity pulldown, Co-IP, immunofluorescence localization, siRNA knockdown with trafficking readout FASEB journal High 33715220
2021 ARFGAP1 promotes constitutive endocytosis of the glutamate transporter EAAT3 via its GAP activity (using ARF6 as substrate) and through a single phenylalanine residue (F508) at the EAAT3 C-terminus; ARFGAP1-promoted AP-2-dependent endocytosis is abolished upon neutralizing F508. Mass spectrometry identification of interaction, knockdown, endocytosis assay, mutagenesis of EAAT3, AP-2 interaction assay Frontiers in physiology Medium 34040545
2014 ARFGAP1 associates transiently with lipid droplets upon oleate addition in hepatocytes; cAMP shifts ARFGAP1 from lipid droplets to the Golgi; ARFGAP1 overexpression and knockdown affect lipid droplet formation. Live-cell imaging, fractionation, overexpression and knockdown with lipid droplet morphology readout PloS one Medium 25397679
2014 Phosphatidic acid generated by PLD2 is required for ArfGAP1 recruitment to Golgi membranes and for formation of specific Golgi tubules; PLD2 inhibition or depletion prevents ArfGAP1 Golgi association. PLD2 inhibitors and siRNA knockdown, ArfGAP1 localization by immunofluorescence PloS one Medium 25354038
2017 ArfGAP1 controls cortical actin cytoskeleton reorganization downstream of Arf1 and PLD1/M3R signaling; silencing ArfGAP1 leads to dysregulated actin dynamics and uncontrolled uptake and replication of Mycobacterium tuberculosis in epithelial cells. siRNA knockdown, actin imaging, infection assay, epistasis with Arf1/PLD1/M3R pathway EMBO reports Medium 29141986
2023 In Drosophila border cells, ArfGAP1 is required to maintain receptor tyrosine kinases (guidance receptors) at the plasma membrane by regulating their endosomal sorting; loss of ArfGAP1 increases active receptors in late endosomes and impairs chemotactic directionality; genetic interactions place ArfGAP1 upstream of Lrrk in receptor sorting. Loss-of-function genetics, fluorescence imaging of receptor localization, endosome/lysosome morphometry, genetic epistasis with Lrrk iScience Medium 37599820
2025 ATG2A localizes to extra-Golgi ARFGAP1-positive puncta during autophagosome biogenesis; ATG2A co-immunoprecipitates with Rab1a at these membranes, and siRNA depletion of Rab1 blocks autophagy downstream of LC3B lipidation similarly to ATG2A depletion, placing ARFGAP1-positive early secretory membranes as a platform for ATG2A-Rab1a engagement in autophagosome formation. Proximity labeling (BioID), co-immunoprecipitation, fluorescence microscopy, siRNA knockdown with autophagy readout bioRxivpreprint Medium 40196537
2026 LRRK2 phosphorylates ArfGAP1 within its ALPS2 motif at Ser284, Thr291, and Thr292; phospho-mimicking mutations redistribute ArfGAP1 from the cis-Golgi to the cytoplasm, impair Golgi-derived vesicle formation, and increase interaction with mitochondrial outer membrane VDACs; blocking phosphorylation protects against G2019S LRRK2-induced neurotoxicity. In vitro phosphorylation, site-directed mutagenesis of phosphosites, subcellular fractionation/imaging, interactome mass spectrometry, vesicle formation assay, primary neuron toxicity assay bioRxivpreprint Medium 41648595
2025 JNK1 phosphorylates the ArfGAP1/GIT1 scaffold protein on S371; dephosphorylated GIT1 enriches in dendritic spines and promotes GABAAR β3 subunit surface expression at extrasynaptic sites and excitatory synapses, increasing inhibitory currents; JNK1 deletion or inhibition increases GABAAR at the plasma membrane in a GIT1-dependent manner. Genetic deletion of JNK1, JNK inhibitor treatment, phospho-site mutagenesis, co-immunoprecipitation, live imaging of GIT1-S371D/A, electrophysiology (sIPSC, tonic current measurement) bioRxivpreprint Medium bio_10.1101_2025.01.22.634236

Source papers

Stage 0 corpus · 41 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 ArfGAP1 responds to membrane curvature through the folding of a lipid packing sensor motif. The EMBO journal 313 15944734
2003 Lipid packing sensed by ArfGAP1 couples COPI coat disassembly to membrane bilayer curvature. Nature 260 14654841
2002 ARFGAP1 promotes the formation of COPI vesicles, suggesting function as a component of the coat. The Journal of cell biology 161 12379802
2001 Sorting of Golgi resident proteins into different subpopulations of COPI vesicles: a role for ArfGAP1. The Journal of cell biology 147 11748249
2005 ARFGAP1 plays a central role in coupling COPI cargo sorting with vesicle formation. The Journal of cell biology 110 15657398
2012 GTPase activity and neuronal toxicity of Parkinson's disease-associated LRRK2 is regulated by ArfGAP1. PLoS genetics 109 22363216
2007 Two lipid-packing sensor motifs contribute to the sensitivity of ArfGAP1 to membrane curvature. Biochemistry 97 17253781
2012 ArfGAP1 is a GTPase activating protein for LRRK2: reciprocal regulation of ArfGAP1 by LRRK2. The Journal of neuroscience : the official journal of the Society for Neuroscience 88 22423108
2005 ArfGAP1 dynamics and its role in COPI coat assembly on Golgi membranes of living cells. The Journal of cell biology 73 15795316
2009 ArfGAP1 generates an Arf1 gradient on continuous lipid membranes displaying flat and curved regions. The EMBO journal 62 19927117
2008 Differential roles of ArfGAP1, ArfGAP2, and ArfGAP3 in COPI trafficking. The Journal of cell biology 61 19015319
2008 ArfGAP1 activity and COPI vesicle biogenesis. Traffic (Copenhagen, Denmark) 43 19055691
2011 ARFGAP1 promotes AP-2-dependent endocytosis. Nature cell biology 37 21499258
2014 Hepatitis C virus NS5A hijacks ARFGAP1 to maintain a phosphatidylinositol 4-phosphate-enriched microenvironment. Journal of virology 34 24623438
2008 Sec24- and ARFGAP1-dependent trafficking of GABA transporter-1 is a prerequisite for correct axonal targeting. The Journal of neuroscience : the official journal of the Society for Neuroscience 30 19020038
2021 ArfGAP1 inhibits mTORC1 lysosomal localization and activation. The EMBO journal 28 33988249
2005 Oligomerization and dissociation of AP-1 adaptors are regulated by cargo signals and by ArfGAP1-induced GTP hydrolysis. Molecular biology of the cell 24 16093346
2012 ArfGAP1 function in COPI mediated membrane traffic: currently debated models and comparison to other coat-binding ArfGAPs. Histology and histopathology 21 22806901
2005 Golgi localization determinants in ArfGAP1 and in new tissue-specific ArfGAP1 isoforms. The Journal of biological chemistry 21 16316994
2017 ArfGAP1 restricts Mycobacterium tuberculosis entry by controlling the actin cytoskeleton. EMBO reports 19 29141986
2011 ArfGAP1 promotes COPI vesicle formation by facilitating coatomer polymerization. Cellular logistics 17 22279613
2010 ArfGAP1 interacts with coat proteins through tryptophan-based motifs. Biochemical and biophysical research communications 17 20211604
2008 Topology of amphipathic motifs mediating Golgi localization in ArfGAP1 and its splice isoforms. The Journal of biological chemistry 17 18195007
2013 Involvement of small ArfGAP1 (SMAP1), a novel Arf6-specific GTPase-activating protein, in microsatellite instability oncogenesis. Oncogene 15 23752192
2011 GAPs: Terminator versus effector functions and the role(s) of ArfGAP1 in vesicle biogenesis. Cellular logistics 15 21686252
2014 ARFGAP1 is dynamically associated with lipid droplets in hepatocytes. PloS one 14 25397679
2021 BPIFB3 interacts with ARFGAP1 and TMED9 to regulate non-canonical autophagy and RNA virus infection. Journal of cell science 10 33277377
2021 ARFGAP1 binds to classical swine fever virus NS5A protein and enhances CSFV replication in PK-15 cells. Veterinary microbiology 10 33721634
2021 Glutamine Regulates Cell Growth and Casein Synthesis through the CYTHs/ARFGAP1-Arf1-mTORC1 Pathway in Bovine Mammary Epithelial Cells. Journal of agricultural and food chemistry 10 34096300
2021 ArfGAP1 acts as a GTPase-activating protein for human ADP-ribosylation factor-like 1 protein. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 8 33715220
2011 The non-catalytic carboxyl-terminal domain of ARFGAP1 regulates actin cytoskeleton reorganization by antagonizing the activation of Rac1. PloS one 8 21483700
2021 Constitutive Endocytosis of the Neuronal Glutamate Transporter Excitatory Amino Acid Transporter-3 Requires ARFGAP1. Frontiers in physiology 7 34040545
2015 Identification of Atg2 and ArfGAP1 as Candidate Genetic Modifiers of the Eye Pigmentation Phenotype of Adaptor Protein-3 (AP-3) Mutants in Drosophila melanogaster. PloS one 7 26565960
2014 Phospholipase D2 is involved in the formation of Golgi tubules and ArfGAP1 recruitment. PloS one 6 25354038
2017 High abundance of ArfGAP1 found in the mossy fibers in hilus of the dentate gyrus region of the mouse brain. PloS one 3 29240824
2018 Detecting phospholipase activity with the amphipathic lipid packing sensor motif of ArfGAP1. Biochemical and biophysical research communications 2 30249399
2025 ATG2A engages Rab1a and ARFGAP1 positive membranes during autophagosome biogenesis. bioRxiv : the preprint server for biology 1 40196537
2023 C9orf72 Toxic Species Affect ArfGAP-1 Function. Cells 1 37566088
2026 LRRK2 regulates ArfGAP1 membrane localization, activity and neuronal toxicity via phosphorylation within its lipid-sensing ALPS2 motif. bioRxiv : the preprint server for biology 0 41648595
2025 ARFGAP1 serves as a critical host factor during E30 infection: QS11 inhibits viral pathogenesis in hFcRn-IFNAR-/- mice. Virology journal 0 41163005
2023 ArfGAP1 regulates the endosomal sorting of guidance receptors to promote directed collective cell migration in vivo. iScience 0 37599820