Ask about this productRelated genes to: RAB35 antibody
- Gene:
- RAB35 NIH gene
- Name:
- RAB35, member RAS oncogene family
- Previous symbol:
- -
- Synonyms:
- H-ray
- Chromosome:
- 12q24.23
- Locus Type:
- gene with protein product
- Date approved:
- 1999-09-29
- Date modifiied:
- 2016-10-05
Related products to: RAB35 antibody
Related articles to: RAB35 antibody
- Neurodevelopmental disorders are increasingly associated with immune phenotypes, including autoinflammation, immunodeficiency, and increased susceptibility to severe infection. To determine whether neurodevelopmental disorders-associated genes exert immune functions, we performed an arrayed siRNA screen targeting 28 genes with nonredundant cellular roles and assessed their effects on Zika virus (ZIKV) infection and innate immune pathways. We identified hits that intrinsically restrict ZIKV infection and modulate inflammatory pathways following infection. We further characterized the antiviral activity of the Hao-Fountain syndrome gene USP7, which potently restricts selected neurotropic orthoflaviviruses. USP7 inhibits ZIKV internalization before viral membrane fusion and genome release into the cytoplasm. Because USP7 plays a role in endosomal tubulation and recycling, we investigated whether endosomal recycling pathways restrict ZIKV infection. We identified the USP7-regulated E3 ubiquitin ligase TRIM27, as well as the recycling-associated Rab GTPases RAB11 and RAB35, as potent regulators of ZIKV infection. Infection assays using cell lines expressing pathogenic USP7 variants and primary fibroblasts from individuals with Hao-Fountain syndrome demonstrated that disease-associated USP7 mutations impair its antiviral activity and increase permissivity to ZIKV infection. These findings are consistent with recent case reports of severe viral infection during early life in individuals with Hao-Fountain syndrome. Collectively, our study identifies endosomal recycling pathways as important intrinsic restriction mechanisms against neurotropic orthoflaviviruses and nominates pathogenic USP7 variation as a candidate inborn error of immunity. - Source: PubMed
Publication date: 2026/09/10
Bonaventure BorisReyes KynaMartin Marie-FrancePan HengRichardson R BlakeBednarski EvaAshbrook Alison WSowa AllisonJanssen WilliamDanzinger OdedCupic AnastasijaMiorin LisaRice Charles MLim Jean KRosenberg Brad REvans Matthew JJohnson Jeffrey R - Epiblast lumen formation is a critical step that occurs during human embryo implantation. It begins with the apicosome, an apical compartment partly derived from endocytosed material. However, how the endo-lysosomal system contributes to apicosome formation and later lumen development remains unclear. Using a human pluripotent stem cell-derived model of epiblast formation, we show that apicosome formation is accompanied by transient expansion of early endosomes, late endosomes, and lysosomes, as well as the formation of hybrid compartments with features of both early and late endo-lysosomal stages. These changes depend on the RAB GTPases RAB35 and RAB7, which are required for proper apicosome formation and lumen morphology of the human epiblast model. Our findings identify RAB35- and RAB7-dependent endo-lysosomal remodeling as a key mechanism driving apical membrane morphogenesis during human epiblast development. - Source: PubMed
Publication date: 2026/08/27
Rengarajan AnushaWang SicongLin Chien-WeiElberfeld Lauren EWettstein Jenna CCarleton Amber ESekulovski NikolaTaniguchi Linnea ESchultz Bailey EDuncan Mara CTaniguchi Kenichiro - LRRK2, the Parkinson's disease-associated kinase, phosphorylates a subset of Rab GTPases and regulates membrane dynamics. We previously reported that lysosomal stress activates LRRK2 and thereby induces the exocytic secretion of lysosomal contents, but the detailed secretion mechanism remained unclear. Here we found that, under lysosomal stress, endolysosomal luminal and membrane components were secreted with extracellular vesicles (EVs) via LRRK2. Bis(monoacylglycerol)phosphate, an endolysosomal lipid and a urinary marker of LRRK2 activity, was similarly secreted via LRRK2, whereas CD9-positive EVs were not involved. Further dissection of the secreted EVs revealed that Alix-positive EVs were secreted via Rab8a as well as the ESCRT component VPS4, whereas LAMP1/cathepsin B-positive EVs were secreted via Rab10/Rab35, and SNARE proteins syntaxin 2 and VAMP8 regulated the secretion of both EV subtypes. These findings suggest a distinctive stress-induced secretory mechanism whereby LRRK2 facilitates the secretion of multiple EV subtypes by controlling Rab GTPases involved in each pathway. - Source: PubMed
Publication date: 2026/08/13
Sakurai MariaKuwahara TomokiSuenaga ShoichiTakatori ShoTomita TaisukeShalit TammyTengstrand ElizabethHsieh FrankIwatsubo Takeshi - Variants in leucine-rich repeat kinase 2 (LRRK2) are the most common genetic cause of Parkinson's disease, yet how these variants alter immune cell function remains unclear. Because LRRK2 is activated by lysosomal damage in macrophages, we investigated how the pathogenic G2019S variant affects macrophage responses to lysosomal damage. Here, we show that LRRK2 G2019S has an effect during lysosomal damage through kinase-dependent and kinase-independent mechanisms. Phosphoproteomic analysis revealed that lysosomal damage induces selective rewiring of LRRK2-dependent Rab GTPase phosphorylation, characterised by increased Rab12 phosphorylation and reduced Rab35 phosphorylation without global kinase hyperactivation. Strikingly, LRRK2 G2019S macrophages showed increased susceptibility to apoptosis following lysosomal damage. This increase in cell death occurred independently of the kinase activity, indicating a distinct kinase-independent role of LRRK2 in regulating cell survival. We generated isogenic induced pluripotent stem cells from patients carrying the LRRK2 G2019S variant and confirmed that LRRK2 G2019S macrophages are more susceptible to cell death in a kinase-independent manner. Together, our findings support a model in which the LRRK2 G2019S variant selectively changes the phosphorylation of Rab GTPases in macrophages and increases cell death after lysosomal damage in macrophages. - Source: PubMed
Publication date: 2026/07/27
Morrison RebeccaMihaylov Simeon RLuk Chak HonLemerle CyrilRodgers AngelaAthanasiadi NataliaMorris Huw RPellegrino EnricaUltanir Sila KGutierrez Maximiliano G - Copper is essential for cellular function but can become toxic in excess. Although its redox and enzymatic roles are well established, how copper availability affects cytoskeletal organization and cell mechanics remains unclear. Here, we show that elevated copper availability increases membrane tether force and F-actin anisotropy in HK-2 proximal tubule cells, consistent with actin cytoskeletal remodeling. Cotreatment with the membrane-permeable reactive oxygen species (ROS) scavenger Tiron reversed copper-induced ROS accumulation and mechanical changes without affecting cell viability, supporting a ROS-dependent mechanism. Quantitative proteomics and post-translational modification profiling (ProteomeXchange: PXD072220) identified coordinated changes in actin-regulatory proteins, including Rab35, methionine sulfoxide reductase B2, casein kinase 2 subunits, and Septin2, together with reduced actin methionine oxidation and copper-sensitive phosphorylation shifts. These findings identify copper-driven redox signaling as a modulator of renal epithelial cell mechanics associated with remodeling of actin-regulatory pathways. Copper-driven redox signaling remodels the actin cytoskeleton and reprograms the mechanical properties of renal proximal tubule cells. Using optical tweezers, fluorescence imaging, quantitative proteomics, and PTM profiling, we link ROS-dependent mechanical changes to coordinated remodeling of the Rab35/MICAL1/MsrB2 and CK2/Septin2 regulatory axes, establishing copper availability as a modulator of renal epithelial cell mechanics with potential relevance to copper dyshomeostasis in kidney injury. - Source: PubMed
Publication date: 2026/07/21
Pompeu PedroSoares JulianaÁvila Dos Santos ÍrisPinheiro Giuliano MartinsDamasceno Nicole JacintoDomingues Romênia RamosGrelle Glória M R SEinicker-Lamas MarceloPontes BrunoValverde Rafael H F