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
- 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 - Porcine hemagglutinating encephalomyelitis virus (PHEV) hijacks lysosomes, repurposing them as vehicles for viral release by disrupting their function. Progranulin (PGRN), a lysosomal glycoprotein essential for lysosomal regulation, plays a pivotal role in this process. This study demonstrates that PHEV infection reduces full-length PGRN levels while enhancing its lysosomal targeting. Notably, PGRN knockout mice exhibit resistance to PHEV infection, implicating PGRN in PHEV-induced lysosomal dysfunction and viral release. Mechanistically, PHEV infection-induced enhancement of PGRN lysosomal trafficking depends on the concurrent harnessing of two distinct pathways for lysosomal delivery of PGRN. This enhanced targeting involves increased vacuolar-type ATPase recruitment, intensifying lysosomal acidification and triggering Arl8b-dependent lysosomal exocytosis, facilitating viral release. Furthermore, knockdown of neuronal PGRN expression suppresses PHEV transmission within the central nervous system. These findings underscore the essential role of PGRN-mediated lysosomal acidification in driving lysosomal exocytosis, thereby contributing to PHEV release and neural dissemination during infection. These insights provide a foundation for targeting PGRN expression and lysosomal trafficking as a potential therapeutic strategy to mitigate PHEV infection and its neural dissemination.IMPORTANCEBetacoronaviruses exploit the lysosomal exocytic pathway for cellular egress through diverse mechanisms, often leading to lysosomal dysfunction. Porcine hemagglutinating encephalomyelitis virus (PHEV), a neurotropic porcine betacoronavirus, relies on lysosomal acidification for cell egress, in contrast to other betacoronaviruses, such as severe acute respiratory syndrome coronavirus 2 and mouse hepatitis virus, which utilize deacidified lysosomes for release. Progranulin (PGRN), a lysosomal glycoprotein essential for regulating lysosomal function, has emerged as a critical player in this process. Here, we demonstrate that PHEV infection enhances PGRN lysosomal trafficking, with PGRN knockout mice exhibiting resistance to PHEV infection. Our findings reveal that PGRN expression and lysosomal targeting drive PHEV-induced lysosomal acidification, facilitating Arl8b-dependent lysosomal exocytosis and promoting viral egress. These results underscore the pivotal role of PGRN in lysosomal dysfunction and viral egress, warranting further investigation into its regulatory function during cellular egress of other betacoronaviruses. - Source: PubMed
Publication date: 2025/11/25
Wang ZhenzhenChen YuzhuHe WenqiLiu YuzhuJiao YuboWang GailiGuan JiyuZhao KuiZhang QiaolingGao FengLi ZiLan Yungang - Osteocytes, the most abundant cells embedded in bone, possess extensive cytoplasmic extensions that form a complex network facilitating direct communication among osteocytes and with other effector cells in the bone and bone marrow. The mechanisms underlying osteocyte dendrite formation during “osteocytogenesis” remain poorly understood. MicroRNAs play a crucial role in regulating bone homeostasis. - Source: PubMed
Publication date: 2025/10/29
Cui YaqiHai BaoHan XiabingLeng HuijieHe DanLu YimengWang HeXu JianZhao Hongshan