Ask about this productRelated genes to: RAB8A antibody
- Gene:
- RAB8A NIH gene
- Name:
- RAB8A, member RAS oncogene family
- Previous symbol:
- MEL
- Synonyms:
- RAB8
- Chromosome:
- 19p13.11
- Locus Type:
- gene with protein product
- Date approved:
- 1986-01-01
- Date modifiied:
- 2016-01-15
Related products to: RAB8A antibody
Related articles to: RAB8A antibody
- Ferroptosis is an iron-dependent form of regulated cell death driven by lipid peroxidation; however, how selective autophagy regulates ferroptotic sensitivity remains incompletely understood. Here, we identify RAB8A as a selective autophagic substrate and negative regulator of ferroptosis. Quantitative proteomic analyses reveal that ferroptotic stress induces ATG5- and ATG7-dependent degradation of RAB8A. Mechanistically, ferroptotic stimuli induce RNF126-dependent polyubiquitination of RAB8A and subsequent SQSTM1-mediated autophagic degradation. Functionally, loss of sensitizes cancer cells to ferroptosis, whereas expression of the degradation-resistant active mutant RAB8A suppresses ferroptotic cell death. RAB8A interacts with TFRC and facilitates stress-induced redistribution of TFRC from the plasma membrane toward endolysosomal compartments. deficiency impairs TFRC clearance, enhances transferrin-dependent iron uptake, and increases intracellular Fe accumulation and lipid peroxidation. In fibrosarcoma and pancreatic cancer xenograft models, depletion enhances the antitumor efficacy of ferroptosis-inducing therapy. Clinically, RAB8A is upregulated and associated with poor prognosis and ferroptosis resistance in pancreatic cancer. Collectively, these findings establish an autophagy-RAB8A-TFRC axis that regulates ferroptotic sensitivity. - Source: PubMed
Publication date: 2026/08/30
Li JingboZhou QileLiu JiaoChen XinYu ChunhuaKang RuiTang Daolin - Despite advances in percutaneous coronary intervention, ischemia-reperfusion (IR) injury remains a major cause of morbidity and mortality. Adiponectin confers broad cardioprotective effects, motivating the development of adiponectin receptor agonists. Here, we investigated the cardioprotective efficacy and mechanisms of ALY688, a synthetic adiponectin receptor agonist peptide, in myocardial IR injury. In a clinically translatable rat IR model, intravenous administration of ALY688 during ischemia together with subcutaneous dosing that continued for 28 days reduced troponin-I levels, cardiomyocyte death, and infarct size, while preserving cardiac function. ALY688 restored autophagic flux, mitigated reactive oxygen species accumulation, and suppressed apoptosis in both IR hearts and hypoxia-reoxygenation (HR)-treated cardiomyocytes. Proteomic profiling revealed that Rab8a, downregulated by IR, was maintained with ALY688 treatment. Notably, ALY688 increased extracellular vesicle (EV) abundance in myocardium and plasma, and EVs from treated animals displayed distinct proteomic signatures enriched in glycolytic and oxidative stress-related proteins. These EVs conferred protection against HR-induced injury in H9c2 and human iPSC-derived cardiomyocytes. CRISPR-mediated Rab8a knockout impaired ALY688-induced EV biogenesis and attenuated the cytoprotective effects of these EVs. Collectively, these findings identify ALY688 as a promising therapeutic that mitigates IR injury via both direct myocardial protection and Rab8a-dependent EV-mediated cardioprotective signalling. - Source: PubMed
Sung Hye KyoungTang JialingLei YubinNguyen KhangTam EddieWu JunLi Ren-KeRichard VincentBorchers Christoph HAntounians LinaBurger DylanZani AugustoSweeney Gary - 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 - Parkinson's disease (PD) pathology extends well beyond dopaminergic neuronal loss, with glial cells-microglia and astrocytes-emerging as active architects of α-synuclein spread rather than passive bystanders. This review synthesises current evidence on how mutations in Leucine-Rich Repeat Kinase 2 (LRRK2), the most common genetic cause of familial PD, fundamentally corrupt glial handling of extracellular α-synuclein. We first outline the biology of extracellular α-synuclein-its cellular sources, conformational spectrum, prion-like propagation mechanisms, and principal glial clearance routes-before examining LRRK2 domain architecture, its downstream Rab GTPase signalling cascade, and the cellular processes it governs in glia. We then detail how LRRK2 mutations reconfigure microglial responses: driving constitutive NLRP3 inflammasome priming, impairing phagolysosomal degradation of α-synuclein aggregates, and redirecting phagocytosed cargo into pathogenic exosomal release via the LRRK2-Rab10-LYTL axis. In astrocytes, LRRK2 mutations disrupt annexin A2-mediated phagocytosis, impair chaperone-mediated autophagy and lysosomal acidification, deplete membrane cholesterol through Rab8A/Rab10 hyperphosphorylation, compromise glutamate transporter surface expression, and promote the secretion of phospho-α-synuclein-enriched extracellular vesicles that are neurotoxic to co-cultured dopaminergic neurons. Crucially, dysfunctional microglia and astrocytes do not operate independently-they form a self-amplifying feed-forward circuit in which microglial cytokines (IL-1α, TNF-α, C1q) drive A1 astrocyte conversion, tunnelling nanotube-mediated aggregate exchange propagates rather than resolves α-synuclein burden, and successive waves of neuronal death perpetuate the cycle. We highlight that these mechanisms are mutation-specific: the GTPase-domain variant I1371V, characterised through our group's patient-derived iPSC platform, drives qualitatively distinct membrane and metabolic dysfunction compared with the kinase-domain variant G2019S, underscoring the need for variant-tailored therapeutic strategies. We review human iPSC-based models-including microglia-like cells, midbrain-patterned astrocytes, and 3D midbrain organoids-that have proven indispensable for resolving cell-autonomous from non-cell-autonomous contributions of LRRK2 mutations. Finally, we evaluate emerging therapeutic strategies targeting LRRK2 kinase activity, NLRP3 inflammasome activation, extracellular α-synuclein immunotherapy, and glial lysosomal enhancement, including intranasal mesenchymal stromal cell-derived small extracellular vesicles. We conclude by identifying key unanswered questions regarding the relative dominance of microglial versus astrocytic clearance at different disease stages, the full pathogenic landscape of understudied LRRK2 variants, and the tractability of glial biomarkers as pharmacodynamic endpoints in clinical trials. - Source: PubMed
Publication date: 2026/06/16
Datta IndraniSahu Dibyam Debasish - Understanding adaptive evolution has long fascinated evolutionary biologists. Adaptive phenotypic divergence is often driven by modifications to protein-coding sequences. The group exhibits relatively lower echolocation frequencies relative to body size compared with other rhinolophids, implying distinct evolutionary trajectories. Transcriptomes bridge genotypes and phenotypes. Here, we sequenced brain, liver and cochlea transcriptomes from one individual per species representing five taxa of the group. We performed comparative transcriptomic analyses and detected signals of positive selection. Seven hearing-related genes (, , , , , and ) were under positive selection. Unexpectedly, we also identified five vision-associated positively selected genes (, , , and ) in taxa with relatively lower echolocation frequencies within the group, indicating selection on sensory genes. Furthermore, candidate positively selected genes were significantly enriched in metabolism-related GO terms such as catalytic and oxidoreductase activity. Our study offers valuable transcriptomic resources for unraveling adaptive genetic mechanisms in horseshoe bats. - Source: PubMed
Publication date: 2026/07/30
Zhang LinSun KepingDai WentaoLiu TongLi AoqiangFeng Jiang