Ask about this productRelated genes to: ARL8B Blocking Peptide
- Gene:
- ARL8B NIH gene
- Name:
- ADP ribosylation factor like GTPase 8B
- Previous symbol:
- ARL10C
- Synonyms:
- FLJ10702, Gie1
- Chromosome:
- 3p26.1
- Locus Type:
- gene with protein product
- Date approved:
- 2004-02-05
- Date modifiied:
- 2017-11-27
Related products to: ARL8B Blocking Peptide
Related articles to: ARL8B Blocking Peptide
- The endolysosomal system is a dynamic intracellular network essential for cargo degradation, recycling, and spatial compartmentalization. Proper coordination of endosome maturation and positioning is critical for lysosomal function and receptor fate. This study identifies an additional role for the E3 ubiquitin ligase RNF13 in controlling endolysosomal dynamics through its interaction with the small GTPase Arl8B. Predictive structural modeling and co-immunoprecipitation revealed that RNF13 binds to Arl8B via residues Glu22 and Phe55 of Arl8B and Leu244 of RNF13. Binding occurs with a modest preference for the GDP-bound Arl8B over GTP-bound state, suggesting that RNF13 may engage an inactive fraction of Arl8B to influence endolysosomal positioning and assembly of Arl8B-dependent trafficking complexes. Disrupting RNF13-Arl8B binding alters Arl8B localization and redistributes lysosomes toward the cell periphery without changing the abundance of endolysosomal markers. Functionally, perturbing this interaction selectively alters epidermal growth factor receptor (EGFR) trafficking kinetics, consistent with a delayed progression of cargo toward lysosomal degradation rather than a general defect in endocytosis. Although overexpression of the Arl8B effector PLEKHM1 enhances RNF13-Arl8B association, this is better explained by a shared Arl8B binding interface and does not imply direct cooperativity between RNF13 and PLEKHM1. Together, these findings identify RNF13 as a regulator of lysosomal organization and cargo transport, operating through Arl8B binding and ubiquitination that can occur without a proportional change in Arl8B abundance under our assay conditions. This work reveals an additional layer of regulation in endolysosomal trafficking, highlighting RNF13 as a regulatory node influencing cargo progression through degradative pathways. - Source: PubMed
Publication date: 2026/05/28
Sénécal Audrey MCabana Valérie CBouchard Antoine YCappadocia LaurentLussier Marc P - The small GTP-binding protein Arl8b is established as a regulator of lysosome positioning and fusion, yet its role in lysosome biogenesis remains unclear. Here, we investigate the role of Arl8b in the trafficking of newly synthesized LAMP1 to lysosomes using the Retention Using Selective Hook (RUSH) assay. We find that Arl8b localizes to post-endocytic LAMP1-containing vesicles prior to fusion with acidic lysosomes. Arl8b depletion leads to Rab11a-dependent recycling of LAMP1 to the plasma membrane, impairing its lysosomal delivery. Mechanistically, Arl8b recruits the Rab11a GAP, TBC1D9B, to LAMP1-positive membranes, and TBC1D9B depletion similarly disrupts LAMP1 sorting. Notably, TBC1D9B knockdown also impairs the retrieval of cation-independent mannose-6-phosphate receptor (CI-M6PR) from Rab11a- and Rab14-positive endosomes to the trans-Golgi network, impairing pro-cathepsin trafficking and cargo degradation. These findings reveal that Arl8b-mediated recruitment of Rab GAP TBC1D9B is crucial for inactivation of the Rab11a recycling pathway, leading to efficient sorting of lysosomal cargo to their functional location. - Source: PubMed
Publication date: 2026/05/21
Chouhan PriyaPhogat YogitaWalia KshitizDebnath SaikatChoubey SandeepGupta MedhaTuli AmitSharma Mahak - Osteoclast-mediated bone resorption depends on the secretion of lysosomal hydrolases via the fusion of secretory lysosomes with the ruffled border, yet the molecular mechanisms governing lysosomal trafficking and fusion remain incompletely understood. Here, we demonstrate that the small GTPase Arl8b regulates the processing of osteoclast-specific lysosomal hydrolase, cathepsin K, and the positioning of secretory lysosomes toward the actin ring. Accordingly, depletion of Arl8b led to defects in lysosome-mediated bone resorption in osteoclasts. We identify RUFY4 as a RANKL-inducible Arl8b effector that promotes lysosome clustering and maturation by linking Arl8b to Rab7 through the adaptor PLEKHM1 and recruiting the multi-subunit tethering factor HOPS complex to drive late endosome-lysosome fusion. Depletion of RUFY4 or HOPS subunits impairs cathepsin K processing and disrupts lysosome positioning, leading to reduced bone resorption activity. These findings suggest that Arl8b and its interaction partners play essential roles in biogenesis and positioning of secretory lysosomes, essential for osteoclast function in bone remodeling. - Source: PubMed
Publication date: 2026/04/02
Walia KshitizKumar GauravArya Subhash BChouhan PriyaKaur ArshdeepGupta MedhaTuli Amit - Lysosomes are highly dynamic organelles that serve antagonistic functions as terminal catabolic stations for the degradation of macromolecules and as central metabolic decision centers for anabolic growth signaling. Lysosome dysfunction is implicated in various human diseases. The physiological roles of lysosomes are linked to the control of lysosome position and dynamics via the activity of the kinesin-activating small GTPase ARL8. How the activity of ARL8 is regulated remains poorly understood. Here, we identify the GTPase-activating Tre-2/Bub2/Cdc16 (TBC) domain protein TBC1D9B as a critical negative regulator of ARL8B function. We demonstrate that TBC1D9B is associated with the lysosomal membrane protein TMEM55B, directly binds to ARL8B-GTP, and stimulates its GTPase activity. Knockout of TBC1D9B or its binding partner TMEM55B causes lysosome dispersion, defective autophagic flux, and impairs the adaptive degradative response of cells to limiting nutrient supply. These lysosomal phenotypes of TBC1D9B loss are occluded by concomitant depletion of ARL8 in cells. Collectively, our data unravel a key role for TBC1D9B in controlling lysosome function by serving as a negative regulator of ARL8 activity. - Source: PubMed
Publication date: 2026/03/14
Duhay ValentinTian MiaomiaoKosieradzka KlaudiaEbner MichaelLo Wen-TingKrauss MichaelSprengel Henner-LinusVoss MatthiasRiechmann MaraSavas Jeffrey NSchwake MichaelHaucke VolkerDamme Markus - Ras-related GTPases are molecular switches regulating hundreds of signaling and trafficking pathways in cells. Many GTPase regulators remain to be identified despite extensive genetic and biochemical screens. Here we present the results of computational protein-protein interaction screens and functional experiments identifying the DENN domain protein Avl9 as a GTPase-activating protein for Arf1. Avl9 is involved in secretion and cell migration, but its molecular function has not been characterized. We determined that Avl9 possesses robust Arf-GAP activity and is recruited to secretory vesicles by Rab8. We find that Avl9 function is conserved in humans and enhances cell migration. We propose that several other DENN domain proteins are also candidate GAPs, and we demonstrate that one candidate previously characterized as a Rab-GEF, DENND6A, exhibits strong Arf-GAP activity towards ARL8B, explaining its role in lysosome positioning. Collectively, this work uncovers a family of monomeric 'DENN GAP' proteins that regulate diverse cell biological pathways. - Source: PubMed
Publication date: 2026/01/05
Vignogna Ryan CFromme J Christopher