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
- 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 - Immune effects of membrane attack complexes (MAC) have been widely attributed to their abilities to cause cell death. Here, we show that the MAC component, C9, forms non-cytolytic aggregates with pro-inflammatory effects. Intracellular aggregates of C9 are detected within inflamed tissues of patients in association with endothelial cell (EC) activation but not increased cell death. We identify NUMBL as a Rab35 effector that directly binds surface-bound C9 to promote C9 internalization and entry into the endolysosomal pathway. Within acidified endolysosomes, C9 forms insoluble aggregates that are targeted for degradative aggrephagy in a process that activates NF-κB. For C9 aggrephagy to occur, ZFYVE21, a Rab5 effector, complexes with RNF34 to bridge C9 aggregates to LC3B+ aggresome membranes. We detect C9 aggregates in vivo, and we show that a ZFYVE21-RNF34 signaling axis is required for C9 aggrephagy and NF-κB -dependent EC activation in three separate mouse models. Mice with conditional loss of ZFYVE21 in ECs show reduced aggregraphy, resulting in attenuated systemic inflammation and reduced tissue injury following skin transplantation. Our data show that the C9 component of MACs forms intracellular aggregates with alarmin-like properties. - Source: PubMed
Publication date: 2026/07/17
Song GuiyuMa ZihanFan MatthewHe LiyingLan YulongLi WeihaoJiang ZhengtaoJiang QuanNoone Dylan PNans AndreaNahas Kamal LBarkestani Mahsa NouriWang ShaoxunWang QianxunRen PengweiCheng JolinZang YinuoZhou HaitianJohnson JustinMullan ClancyGong XiangyuBubeck DoryenMoeckel GilbertMak MichaelTellides GeorgeJane-Wit Dan - Cell wound repair requires rapid and coordinated remodeling of the actin cytoskeleton to restore cortex integrity. Here, we show that a Rab35-Mical-SelR pathway regulates actomyosin ring dynamics through reversible actin redox. We find that Rab35 is recruited to wounds and is essential for proper actin ring assembly and disassembly. Rab35 regulates the recruitment of Mical, an actin-oxidizing enzyme, and SelR, a reductase that reverses oxidation, to the cell wound. Mical and SelR knockdowns disrupt actin ring formation and wound closure, whereas double knockdown partially rescues these defects, indicating a balanced redox cycle is required. Super-resolution microscopy reveals that Mical and SelR differentially regulate F-actin architecture and orientation. Mutation of actin at Methionine 44 does not fully recapitulate Mical knockdown phenotypes, suggesting the presence of additional targets and enzymes. Taken together, our results indicate that reversible actin modifications dynamically regulate F-actin architecture and orientation for actin ring assembly and disassembly. - Source: PubMed
Publication date: 2026/07/06
Nakamura MitsutoshiHui JustinParkhurst Susan M