Affinage

ARL8B

ADP-ribosylation factor-like protein 8B · UniProt Q9NVJ2

Length
186 aa
Mass
21.5 kDa
Annotated
2026-06-09
27 papers in source corpus 26 papers cited in narrative 27 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ARL8B is a lysosome-resident Arf-like GTPase that functions as a master organizer of lysosomal positioning, fusion, biogenesis, and immune function (PMID:16650381, PMID:21802320). In its GTP-bound state it localizes to lysosomal membranes, and constitutively active mutants redistribute lysosomes to the cell periphery, establishing GTP-dependent control of lysosomal spatial distribution (PMID:16650381). ARL8B drives anterograde, centrifugal lysosome transport by assembling a tripartite ARL8B–SKIP–kinesin-1 (KIF5B) complex, with SKIP also recruiting kinesin-3 (KIF1Bβ) to a subset of lysosomes (PMID:24088571, PMID:34878110). Opposing retrograde transport is coordinated through effectors RUFY3, which couples ARL8B to the JIP4–dynein–dynactin complex, and DENND6A, a GEF that activates Rab34 to recruit a RILP/dynein complex (PMID:35314681, PMID:38296963). ARL8B also recruits the HOPS tethering complex to lysosomes—it is essential for membrane localization of the HOPS subunit hVps41/VPS41 (via its WD40 domain), enabling late endosome–lysosome fusion, endocytic cargo degradation including EGFR, and recruitment of TGN-derived biosynthetic LAMP carriers (PMID:21802320, PMID:25908847, PMID:39907656). Beyond degradative trafficking, ARL8B governs lysosomal cargo delivery by controlling endosomal recycling machinery: it recruits the Rab11a GAP TBC1D9B and determines the localization of RUFY1 and the retrieval of CI-M6PR, biasing cargo toward lysosomal delivery rather than plasma-membrane recycling (PMID:36282215, PMID:42166252). In the GDP-bound conformation an exposed N-terminal amphipathic helix targets ARL8B to lipid droplets, where it mediates LD–lysosome contacts and lipid transfer as a major lipolytic route in macrophages (PMID:37777960). These activities underlie diverse cellular and immune processes including HOPS-dependent antigen presentation, NK-cell lytic granule polarization, lysosomal exocytosis for plasma-membrane repair, embryonic maternal-protein degradation, and axon-branch positioning (PMID:21802320, PMID:24088571, PMID:28827407, PMID:29592961, PMID:32917789). ARL8B activity is tuned by upstream BORC/lyspersin, which loads ARL8B onto lysosomes and is antagonized by LAMTOR, and by post-translational modifications: NatC-mediated N-terminal acetylation and RNF167/RNF13-mediated ubiquitination at K141 that target it for degradation (PMID:19398576, PMID:27808481, PMID:28993467, PMID:42206902).

Mechanistic history

Synthesis pass · year-by-year structured walk · 25 steps
  1. 2006 Medium

    Established that ARL8B is a lysosomal GTPase whose activity dictates organelle positioning, answering whether it has a defined subcellular role.

    Evidence Confocal immunofluorescence with a GTP-restricted mutant showing lysosome redistribution to the periphery

    PMID:16650381

    Open questions at the time
    • No molecular effectors of the positioning identified
    • GTP-loading mechanism not addressed
  2. 2009 Medium

    Showed ARL8B is regulated post-translationally, identifying NatC-mediated N-terminal acetylation as a determinant of its localization.

    Evidence In vitro acetyltransferase assay plus hMAK3 knockdown with localization imaging

    PMID:19398576

    Open questions at the time
    • Functional consequence of mis-localization not quantified
    • Direct acetylation of ARL8B not shown in cells
  3. 2011 High

    Defined the ARL8B–HOPS axis and ARL8B's requirement for lysosomal cargo delivery, linking the GTPase to membrane fusion machinery and immune trafficking.

    Evidence shRNA screen, RNAi, phagosome-lysosome fusion and CD1 antigen presentation assays

    PMID:21802320

    Open questions at the time
    • Which HOPS subunit directly binds ARL8B not resolved here
    • Anterograde motor link not yet established
  4. 2011 Medium

    Revealed ARL8B is hijacked by pathogens to drive vacuole motility, demonstrating its kinesin-recruitment function in an infection context.

    Evidence Salmonella infection model with RNAi and kinesin-1 recruitment imaging

    PMID:21824248

    Open questions at the time
    • Direct ARL8B-kinesin interaction not biochemically shown
    • Adaptor between ARL8B and kinesin-1 not identified
  5. 2013 High

    Identified the ARL8B–SKIP–kinesin-1 (KIF5B) tripartite complex and its role in NK-cell cytotoxicity, providing the biochemical basis for anterograde movement.

    Evidence GST pull-down for KIF5B interaction plus shRNA, granule polarization and cytotoxicity assays

    PMID:24088571

    Open questions at the time
    • Stoichiometry/structure of the tripartite complex unresolved
    • Regulation of complex assembly not defined
  6. 2015 High

    Established that ARL8B is required for membrane localization of HOPS subunit hVps41 and downstream EGFR degradation, ordering the ARL8B–SKIP–HOPS hierarchy.

    Evidence RNAi, Arl8b-binding-defective hVps41 rescue, EGFR degradation assay, co-IP

    PMID:25908847

    Open questions at the time
    • Direct ARL8B-hVps41 binding interface not mapped here
    • Rab7-independence mechanism not fully explained
  7. 2015 Medium

    Extended ARL8B function to adaptive immunity, showing it regulates MHC class II–peptide complex formation and delivery for T-cell activation.

    Evidence RNAi silencing in dendritic cells with MHC II complex and T-cell activation assays

    PMID:25637027

    Open questions at the time
    • Molecular effectors in MHC II compartment not identified
    • Link to HOPS/fusion machinery not tested
  8. 2016 Medium

    Connected ARL8B-driven anterograde lysosome positioning to extracellular cues and invasive cancer phenotypes.

    Evidence RNAi, 3D invasion and lysosome positioning assays, xenograft model

    PMID:27105540

    Open questions at the time
    • Signaling pathway from receptors to ARL8B not mapped here
    • Protease/cargo identity in ECM degradation not defined
  9. 2016 High

    Identified RNF167-mediated ubiquitination of ARL8B at K141 as a degradative regulatory input controlling its protein level and positioning function.

    Evidence BioID, ubiquitination assay, K141R mutagenesis, lysosome positioning and trafficking assays

    PMID:27808481

    Open questions at the time
    • Deubiquitinase counterpart not identified
    • Signals triggering RNF167 activity unknown
  10. 2017 High

    Mapped the upstream loading machinery, showing BORC/lyspersin recruits ARL8B to lysosomes and LAMTOR antagonizes this in a growth-factor-responsive manner.

    Evidence Domain deletion, co-IP, lysosome positioning, EGF stimulation

    PMID:28993467

    Open questions at the time
    • GEF that loads GTP onto ARL8B not identified
    • Direct lyspersin-ARL8B contact not biochemically defined
  11. 2017 High

    Demonstrated ARL8B's physiological role in lysosomal degradation during development using genetic mouse models.

    Evidence Gene-trap and conditional KO mice, immunofluorescence, free amino acid measurement

    PMID:28827407

    Open questions at the time
    • Tissue-specific effectors not dissected
    • Mechanism of cargo accumulation step not pinpointed
  12. 2018 Medium

    Showed ARL8B drives lysosomal exocytosis for plasma-membrane repair, determining macrophage cell-death fate during infection.

    Evidence RNAi, membrane repair and exocytosis assays, M. tuberculosis macrophage model

    PMID:29592961

    Open questions at the time
    • Exocytic fusion machinery downstream of ARL8B not defined
    • Ca2+-trigger link not addressed
  13. 2019 Medium

    Revealed pathogen manipulation of ARL8B abundance and positioning to suppress autophagic flux.

    Evidence RNAi, tandem RFP-GFP-LC3 flux assay, in vitro vesicle fusion assay (HCV model)

    PMID:31383738

    Open questions at the time
    • Mechanism of HCV-induced ARL8B upregulation unknown
    • Whether fusion machinery is directly affected unclear
  14. 2019 Medium

    Linked ARL8B loss to dorsal neural tube development and BMP signaling, extending its role to morphogenesis.

    Evidence Gene-trap KO mice, IHC, in situ hybridization, BMP pathway western blots

    PMID:31038803

    Open questions at the time
    • BMP pathway placement is correlative, not directly tested
    • Lysosomal mechanism connecting ARL8B to BMP signaling unknown
  15. 2020 Medium

    Established that ARL8B controls neuronal axon branch density and position by spatially distributing lysosomes and autophagosomes.

    Evidence shRNA, overexpression, in vivo atg7 conditional KO, rapamycin treatment in retinal ganglion cells

    PMID:32917789

    Open questions at the time
    • Molecular link between lysosome position and branching unresolved
    • Effector specificity in neurons not defined
  16. 2020 Medium

    Connected radiation-induced ARL8B–SKIP binding and BORC regulation to lysosomal exocytosis and cancer invasiveness/metastasis.

    Evidence Co-IP, RNAi, exocytosis assay, in vivo tumor model

    PMID:33110168

    Open questions at the time
    • Signaling upstream of increased ARL8B-SKIP binding unclear
    • Exocytic cargo driving invasion not identified
  17. 2022 High

    Identified RUFY3 as an ARL8B effector coupling the GTPase to the JIP4–dynein–dynactin retrograde motor, defining a bidirectional positioning system.

    Evidence Reciprocal co-IP, RNAi, positioning and colocalization imaging, PIKFYVE rescue

    PMID:35314681

    Open questions at the time
    • Switch between RUFY3 and anterograde adaptors not defined
    • Direct dynein-RUFY3 contact specifics not resolved
  18. 2022 High

    Showed ARL8B controls RUFY1 endosomal localization and CI-M6PR retrieval, expanding its role to endosome-to-TGN cargo retrieval.

    Evidence Co-IP, RNAi, CI-M6PR trafficking and dynein interaction assays, EM

    PMID:36282215

    Open questions at the time
    • How ARL8B regulates RUFY1-Rab14 interaction mechanistically unclear
    • Relationship between RUFY1 and RUFY3 pathways undefined
  19. 2024 High

    Defined the ARL8B→DENND6A→Rab34→RILP/dynein retrograde cascade governing nutrient-dependent juxtanuclear lysosome repositioning.

    Evidence Cell-based GEF activity assay, co-IP, loss-of-function, positioning and autophagic flux assays

    PMID:38296963

    Open questions at the time
    • Coordination with the RUFY3 retrograde route unresolved
    • Nutrient-sensing input to ARL8B not mapped
  20. 2024 Medium

    Linked ARL8B to RAB2A activation and MAPK/ERK signaling in hepatocellular carcinoma, suggesting a signaling role beyond trafficking.

    Evidence Mass spectrometry, co-IP, GTP-RAB2A pull-down, ERK phosphorylation assay

    PMID:39413890

    Open questions at the time
    • Mechanistic link between ARL8B and ERK via RAB2A not fully validated
    • Whether ARL8B acts as a RAB2A GEF unknown
  21. 2023 High

    Discovered the GDP-conformation-dependent lipid-droplet localization of ARL8B and its role in LD–lysosome lipid transfer, revealing a second organelle function.

    Evidence Fluorescence microscopy, GDP/GTP conformational analysis, contact-site and lipid-transfer assays in macrophages

    PMID:37777960

    Open questions at the time
    • Lipid-transfer protein partner at the contact not identified
    • Switch between LD and lysosome pools in vivo not quantified
  22. 2025 High

    Extended VPS41-ARL8B interaction to biosynthetic LAMP carrier trafficking, mapping the WD40 domain as the binding determinant.

    Evidence Ectopic VPS41 mis-targeting, RUSH LAMP tracking, EM, binding assay

    PMID:39907656

    Open questions at the time
    • Regulation of carrier vs fusion VPS41 functions undefined
    • Whether other HOPS subunits are involved in carrier capture unclear
  23. 2023 Medium

    Showed ARL8B interacts with RAB5A to promote ITGB1 endosomal recycling and FAK signaling in osteocytes, defining a cargo-protective trafficking role.

    Evidence Co-IP, GST pull-down, lysosome IP, surface biotinylation, ITGB1 trafficking assay

    PMID:41163020

    Open questions at the time
    • Direct vs indirect ARL8B-RAB5A interaction not fully resolved
    • Mechanism diverting ITGB1 from degradation unclear
  24. 2026 High

    Demonstrated ARL8B recruits the Rab11a GAP TBC1D9B to bias cargo from plasma-membrane recycling toward lysosomal delivery, integrating it with recycling control.

    Evidence RUSH assay, RNAi, GAP recruitment, LAMP1 and CI-M6PR trafficking assays

    PMID:42166252

    Open questions at the time
    • Direct ARL8B-TBC1D9B binding interface not mapped
    • Coordination with RUFY1 retrieval pathway unresolved
  25. 2026 Medium

    Identified RNF13 as a second E3 ligase binding ARL8B and controlling its degradation and lysosome positioning, refining the ubiquitin-regulation model.

    Evidence Predictive structural modeling, co-IP, residue-level mutagenesis (Glu22/Phe55), positioning and EGFR trafficking assays

    PMID:42206902

    Open questions at the time
    • Structural model is predictive, not experimentally determined
    • Overlap/redundancy with RNF167 not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple ARL8B effector arms (SKIP-kinesin, RUFY3, DENND6A-Rab34, RUFY1, TBC1D9B) are dynamically coordinated, and the identity of the GEF that loads GTP onto lysosomal ARL8B, remain open.
  • No ARL8B GEF identified in the corpus
  • Mechanism switching anterograde vs retrograde effector selection undefined
  • Integration of signaling (RAB2A/ERK) and trafficking functions unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 3 GO:0060090 molecular adaptor activity 3 GO:0003924 GTPase activity 2 GO:0008289 lipid binding 1
Localization
GO:0005764 lysosome 3 GO:0005768 endosome 3 GO:0005811 lipid droplet 1 GO:0005886 plasma membrane 1
Pathway
R-HSA-5653656 Vesicle-mediated transport 5 R-HSA-168256 Immune System 4 R-HSA-9609507 Protein localization 3 R-HSA-9612973 Autophagy 3 R-HSA-1430728 Metabolism 2
Partners
DENND6AKIF5BRNF13RNF167RUFY1RUFY3TBC1D9BVPS41
Complex memberships
ARL8B-SKIP-kinesin-1 complexBORC (upstream loading)HOPS complex (effector)

Evidence

Reading pass · 27 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 ARL8B (Arl8b) localizes to lysosomal membranes and a GTP-restricted (constitutively active) mutant of Arl8b redistributes lysosomes to the cell periphery and into membrane projections, indicating Arl8b controls lysosomal spatial distribution via GTP-dependent activity. Confocal immunofluorescence microscopy, GTP-restricted mutant expression, co-localization with lysosomal markers Biochemical and biophysical research communications Medium 16650381
2009 The human NatC complex (hNatC), containing catalytic subunit hMak3, acetylates Met-Leu protein N-termini in vitro; knockdown of hMAK3 alters subcellular localization of ARL8B, supporting ARL8B as an in vivo substrate of hNatC-mediated N-terminal acetylation. In vitro acetyltransferase assay, siRNA knockdown, subcellular localization imaging Molecular and cellular biology Medium 19398576
2011 Arl8b is required for cargo delivery to lysosomes; HOPS complex members (homotypic fusion and vacuole protein sorting complex) are effectors of Arl8b and depend on Arl8b for their recruitment to lysosomes, establishing an Arl8b-HOPS axis that directs lysosomal trafficking. shRNA library screen, RNAi knockdown, immunofluorescence co-localization, phagosome-lysosome fusion assay, CD1 antigen presentation assay Immunity High 21802320
2011 Salmonella exploits Arl8b on Salmonella-containing vacuoles (SCVs) to recruit kinesin-1, driving tubulated endosome (SIF) formation, SCV migration to the cell periphery, and cell-to-cell bacterial transfer. Bacterial infection model, RNAi knockdown, immunofluorescence for kinesin-1 recruitment, LAMP1-tubule formation assay Cellular microbiology Medium 21824248
2013 Arl8b is required for NK cell cytotoxicity by driving polarization of lytic granules and MTOCs toward the immune synapse; kinesin-1 heavy chain KIF5B was identified as an Arl8b interaction partner via GST pull-down, and the Arl8b–SKIP–kinesin-1 tripartite complex mediates anterograde granule movement. GST pull-down, shRNA knockdown, lytic granule polarization assay, cytotoxicity assay Molecular biology of the cell High 24088571
2015 Arl8b, but not Rab7, is essential for membrane localization of hVps41, the HOPS complex subunit; Arl8b-dependent lysosomal localization of hVps41 is required for EGFR endocytic degradation, as an Arl8b-binding-defective mutant of hVps41 fails to rescue EGFR degradation. Additionally, Arl8b effector SKIP interacts with and recruits HOPS subunits to peripheral lysosomes. RNAi depletion, rescue with Arl8b-binding-defective mutant, EGFR degradation assay, co-immunoprecipitation Journal of cell science High 25908847
2015 Arl8b localizes to MHC class II compartments in dendritic cells and regulates formation of MHC II–peptide complexes and their delivery to the plasma membrane for T cell activation. RNAi silencing, immunofluorescence localization, MHC II–peptide complex formation assay, T cell activation assay Journal of immunology Medium 25637027
2016 Arl8b regulates anterograde lysosome trafficking to the cell periphery in response to HGF, EGF, and acidic extracellular pH; depletion of Arl8b impairs invasive growth and proteolytic ECM degradation in 3D prostate cancer models and abolishes xenograft formation in mice. RNAi knockdown, 3D invasion assay, lysosome positioning assay, xenograft mouse model Oncotarget Medium 27105540
2016 RNF167, a RING-domain E3 ubiquitin ligase, ubiquitinates Arl8B at lysine K141, reducing Arl8B protein levels; RNF167 overexpression/knockdown correspondingly alters Arl8b-dependent lysosome positioning and endocytic trafficking, and an ubiquitination-defective Arl8B K141R mutant counteracts RNF167 effects. Proximity-dependent biotin labeling (BioID), ubiquitination assay, site-directed mutagenesis (K141R), lysosome positioning assay, endocytic trafficking assay The FEBS journal High 27808481
2017 The C-terminal domain of lyspersin (a BORC subunit) is essential and sufficient for BORC-dependent recruitment of Arl8b to lysosomes; LAMTOR negatively regulates this process by associating with BORC, and EGF stimulation reduces LAMTOR/BORC association to promote Arl8b-dependent centrifugal lysosomal transport. Domain deletion analysis, co-immunoprecipitation, lysosome positioning assay, EGF stimulation The Journal of cell biology High 28993467
2017 Arl8b is required for lysosomal degradation of maternal proteins in the visceral yolk sac endoderm; Arl8b gene-trap and conditional knockout mice show defective endocytic trafficking to lysosomes, accumulation of maternal proteins (albumin, IgG) in late endocytic organelles, reduced free amino acids in embryos, and decreased embryo body size. Gene-trap mouse model, conditional knockout (Transthyretin-Cre), immunofluorescence, free amino acid measurement Journal of cell science High 28827407
2018 Arl8b is required for lysosomal exocytosis-mediated plasma membrane repair; Arl8b-depleted cells fail to repair plasma membrane damage induced by M. tuberculosis, causing necrosis instead of apoptosis in macrophages infected with avirulent H37Ra. RNAi knockdown, plasma membrane repair assay, lysosomal exocytosis assay, macrophage infection model Journal of immunology Medium 29592961
2019 HCV infection increases Arl8b expression ~3-fold and redistributes it to a peripheral pattern that fails to co-localize with LC3-positive autophagosomes; knockdown of Arl8b in HCV-infected cells restores autophagosome-lysosome fusion and autophagic flux, demonstrating that HCV suppresses autophagic flux by upregulating and repositioning Arl8b. RNAi knockdown, tandem RFP-GFP-LC3 autophagic flux assay, in vitro vesicle fusion assay, immunofluorescence The Journal of biological chemistry Medium 31383738
2019 Loss of Arl8b in mice disrupts dorsal neural tube development, including ectopic Sox1 expression in the roof plate and elevated BMP receptor IA and phospho-Smad 1/5/8 signaling in the neural fold, suggesting Arl8b regulates BMP signaling during neural tube development. Gene-trap knockout mice, immunohistochemistry, in situ hybridization, western blot for BMP pathway components Genes to cells Medium 31038803
2020 Arl8b controls density and position of interstitial axon branches in retinal ganglion cells by spatially controlling the location and density of lysosomes and autophagosomes along the axon shaft; Arl8b downregulation reduces branch density and shifts branches proximally, while overexpression increases density and positions branches more distally. shRNA knockdown, overexpression, immunofluorescence, in vivo conditional knockout (atg7), rapamycin treatment The Journal of neuroscience Medium 32917789
2020 Arl8b binding to its effector SKIP is increased after radiation through regulation of BORC subunits; Arl8b and BORC-mediated lysosomal exocytosis drives invasiveness of radiation-surviving cancer cells, and in vivo Arl8b ablation decreases IR-induced invasive tumor growth and metastasis. Co-immunoprecipitation, RNAi knockdown, lysosomal exocytosis assay, in vivo mouse tumor model Communications biology Medium 33110168
2022 RUFY3 is an Arl8b effector that regulates retrograde lysosomal transport; RUFY3 interacts with the JIP4-dynein-dynactin complex and facilitates Arl8b association with the retrograde motor complex. RUFY3 knockdown disrupts Arl8b-positive endosome positioning, reduces Arl8b colocalization with Rab7-marked compartments, and reduces lysosome size (rescued by PIKFYVE inhibition). Co-immunoprecipitation, RNAi knockdown, lysosome positioning assay, co-localization imaging, PIKFYVE inhibitor rescue Nature communications High 35314681
2022 Arl8b binds RUFY1 and determines RUFY1 endosomal localization by regulating its interaction with Rab14; RUFY1 mediates endosome-to-TGN retrieval of CI-M6PR via the dynein-dynactin complex, and RUFY1 depletion delays CI-M6PR retrieval and impairs lysosomal cargo (cathepsin) delivery. Co-immunoprecipitation, RNAi depletion, CI-M6PR trafficking assay, dynein interaction assay, electron microscopy The Journal of cell biology High 36282215
2022 The Salmonella effector SifA mimics the Arl8a/Arl8b-SKIP pathway by recruiting kinesin-1 and kinesin-3 (KIF1Bβ) to Salmonella vacuoles; in the non-infectious context, SKIP is essential for kinesin-3 recruitment to a fraction of lysosomes downstream of Arl8b. Bacterial infection model, co-immunoprecipitation, kinesin recruitment assay, vacuole stability assay Journal of cell science Medium 34878110
2023 ARL8B-GDP localizes to lipid droplets (LDs) via an exposed N-terminal amphipathic helix induced by GDP binding; ARL8B-GTP predominantly localizes to lysosomes. By associating with both organelles, ARL8B mediates LD-lysosome contacts and lipid transfer, serving as the major lipolytic pathway in human macrophages. Fluorescence microscopy, GDP/GTP conformational analysis, LD-lysosome contact site assay, lipid transfer assay, macrophage functional assay Cell reports High 37777960
2024 DENND6A is an Arl8b effector; Arl8b recruits DENND6A to peripheral lysosomes where DENND6A acts as a GEF activating Rab34, which then recruits a RILP/dynein complex to initiate lysosomal retrograde transport, regulating nutrient-dependent juxtanuclear lysosome repositioning and autophagic flux. GEF activity assay (cell-based), co-immunoprecipitation, loss-of-function, lysosome positioning assay, autophagic flux assay Nature communications High 38296963
2024 ARL8B directly interacts with RAB2A (shown by mass spectrometry and co-IP) and increases GTP-bound RAB2A levels, activating the MAPK/ERK signaling pathway in hepatocellular carcinoma cells. Mass spectrometry, co-immunoprecipitation, GTP-RAB2A pull-down, ERK phosphorylation assay Cellular signalling Medium 39413890
2025 VPS41 binds Arl8b via its WD40 domain; Arl8b is present on TGN-derived LAMP carriers and enables their recruitment by VPS41, expanding VPS41-Arl8b interactions beyond endosome-lysosome fusion to include biosynthetic LAMP carrier trafficking. Mitochondria mis-targeting (ectopic VPS41), RUSH system for newly synthesized LAMP tracking, electron microscopy, co-IP/binding assay The Journal of cell biology High 39907656
2025 ARL8B interacts with RAB5A (identified by co-IP and GST pull-down); ARL8B promotes RAB5A-mediated ITGB1 endosomal recycling and prevents ITGB1 lysosomal degradation, thereby maintaining ITGB1 levels and FAK signaling to support osteocyte dendritic process formation. Co-immunoprecipitation, GST pull-down, lysosome immunoprecipitation, cell surface biotinylation, ITGB1 trafficking assay Stem cell research & therapy Medium 41163020
2026 Arl8b localizes to post-endocytic LAMP1-containing vesicles and recruits the Rab11a GAP TBC1D9B to LAMP1-positive membranes, inactivating the Rab11a recycling pathway; without Arl8b, LAMP1 undergoes Rab11a-dependent recycling to the plasma membrane instead of lysosomal delivery. TBC1D9B knockdown also impairs CI-M6PR retrieval from Rab11a/Rab14 endosomes to the TGN, impairing cathepsin delivery. RUSH assay, RNAi depletion, Rab11a GAP recruitment assay, LAMP1 trafficking assay, CI-M6PR retrieval assay The Journal of cell biology High 42166252
2026 RNF13 binds Arl8B via residues Glu22 and Phe55 of Arl8B (and Leu244 of RNF13) with modest preference for GDP-bound Arl8B; disrupting this interaction redistributes lysosomes to the cell periphery and selectively delays EGFR trafficking toward lysosomal degradation. Predictive structural modeling, co-immunoprecipitation, site-directed mutagenesis, lysosome positioning assay, EGFR trafficking assay The FEBS journal Medium 42206902
2025 RNF13 mediates ubiquitin-dependent degradation of ARL8B; RNF13 activity is regulated by intracellular pH and Ca2+-bound ALG-2 (apoptosis-linked gene 2). Elevated pH_i deprotonates RNF13 at His332, enabling ALG-2 interaction and RNF13 activation, which reduces ARL8B levels and inhibits anterograde lysosomal transport; alkaline extracellular pH elevates lysosomal Ca2+ via TRPML3, further activating RNF13. pH manipulation, Ca2+ signaling assay, ubiquitination assay, lysosome positioning assay, RNF13 mutagenesis (His332), co-immunoprecipitation bioRxivpreprint Medium

Source papers

Stage 0 corpus · 27 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2011 Lysosomal trafficking, antigen presentation, and microbial killing are controlled by the Arf-like GTPase Arl8b. Immunity 157 21802320
2015 The small GTPase Arl8b regulates assembly of the mammalian HOPS complex on lysosomes. Journal of cell science 126 25908847
2009 Knockdown of human N alpha-terminal acetyltransferase complex C leads to p53-dependent apoptosis and aberrant human Arl8b localization. Molecular and cellular biology 99 19398576
2017 LAMTOR/Ragulator is a negative regulator of Arl8b- and BORC-dependent late endosomal positioning. The Journal of cell biology 91 28993467
2006 The Arf-family protein, Arl8b, is involved in the spatial distribution of lysosomes. Biochemical and biophysical research communications 84 16650381
2022 RUFY3 links Arl8b and JIP4-Dynein complex to regulate lysosome size and positioning. Nature communications 68 35314681
2013 Arf-like GTPase Arl8b regulates lytic granule polarization and natural killer cell-mediated cytotoxicity. Molecular biology of the cell 60 24088571
2016 The Arf-like GTPase Arl8b is essential for three-dimensional invasive growth of prostate cancer in vitro and xenograft formation and growth in vivo. Oncotarget 53 27105540
2011 Salmonella exploits Arl8B-directed kinesin activity to promote endosome tubulation and cell-to-cell transfer. Cellular microbiology 42 21824248
2020 Lysosomal trafficking mediated by Arl8b and BORC promotes invasion of cancer cells that survive radiation. Communications biology 41 33110168
2023 ARL8B mediates lipid droplet contact and delivery to lysosomes for lipid remobilization. Cell reports 32 37777960
2018 Lysosome-Mediated Plasma Membrane Repair Is Dependent on the Small GTPase Arl8b and Determines Cell Death Type in Mycobacterium tuberculosis Infection. Journal of immunology (Baltimore, Md. : 1950) 30 29592961
2015 MHC class II presentation is controlled by the lysosomal small GTPase, Arl8b. Journal of immunology (Baltimore, Md. : 1950) 30 25637027
2023 A proteomics analysis of 5xFAD mouse brain regions reveals the lysosome-associated protein Arl8b as a candidate biomarker for Alzheimer's disease. Genome medicine 29 37468900
2016 RNF167 targets Arl8B for degradation to regulate lysosome positioning and endocytic trafficking. The FEBS journal 24 27808481
2017 Arl8b is required for lysosomal degradation of maternal proteins in the visceral yolk sac endoderm of mouse embryos. Journal of cell science 22 28827407
2019 Hepatitis C virus infection increases autophagosome stability by suppressing lysosomal fusion through an Arl8b-dependent mechanism. The Journal of biological chemistry 21 31383738
2024 DENND6A links Arl8b to a Rab34/RILP/dynein complex, regulating lysosomal positioning and autophagy. Nature communications 17 38296963
2022 RUFY1 binds Arl8b and mediates endosome-to-TGN CI-M6PR retrieval for cargo sorting to lysosomes. The Journal of cell biology 16 36282215
2020 The GTPase Arl8B Plays a Principle Role in the Positioning of Interstitial Axon Branches by Spatially Controlling Autophagosome and Lysosome Location. The Journal of neuroscience : the official journal of the Society for Neuroscience 10 32917789
2025 VPS41 recruits biosynthetic LAMP-positive vesicles through interaction with Arl8b. The Journal of cell biology 7 39907656
2022 The Salmonella effector SifA initiates a kinesin-1 and kinesin-3 recruitment process mirroring that mediated by Arl8a and Arl8b. Journal of cell science 7 34878110
2024 ARL8B promotes hepatocellular carcinoma progression and inhibits antitumor activity of lenvatinib via MAPK/ERK signaling by interacting with RAB2A. Cellular signalling 4 39413890
2019 Loss of the small GTPase Arl8b results in abnormal development of the roof plate in mouse embryos. Genes to cells : devoted to molecular & cellular mechanisms 1 31038803
2026 Arl8b inactivates the Rab11a recycling pathway to promote LAMP1 sorting and lysosome biogenesis. The Journal of cell biology 0 42166252
2026 RNF13 regulates the endolysosomal pathway through interaction with the small GTPase Arl8B. The FEBS journal 0 42206902
2025 Depletion of mmu-miR-185 enhances osteocyte connectivity and suppresses bone fragility through the interaction between ARL8B and RAB5A. Stem cell research & therapy 0 41163020

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