RAB8A Mouse Monoclonal Antibody
- Known as:
- RAB8A Mouse Monoclonal Antibody
- Catalog number:
- BIN-004218-M02
- Product Quantity:
- 0.1mg
- Category:
- -
- Supplier:
- Zyagen
- Gene target:
- RAB8A Mouse Monoclonal Antibody
Related genes to: RAB8A Mouse Monoclonal 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 Mouse Monoclonal Antibody
Related articles to: RAB8A Mouse Monoclonal Antibody
- Microglia are critical regulators of neuroinflammation and neurodegeneration. Haploinsufficiency of C9orf72, the most frequently mutated gene in amyotrophic lateral sclerosis and frontotemporal dementia, has been linked to autophagy-lysosomal pathway defects, but the role of C9orf72 in microglia remains unclear. Here, we identify the C9orf72/SMCR8 complex as a key regulator of microglial homeostasis through promoting lysosomal membrane repair. Loss of C9orf72 and SMCR8 in mice causes age‑dependent neuroinflammation and microgliosis, with microglia adopting a disease-associated state. In aged brain and spinal cord tissue, microglia display lysosomal damage marked by galectin‑3 accumulation. Using a lysosomotropic agent to induce lysosomal damage in microglia, we find that C9orf72/SMCR8-deficient cells accumulate damaged lysosomes and show defective recruitment of phosphorylated RAB8A and the Endosomal Sorting Complexes Required for Transport (ESCRT) machinery to damaged lysosomes. Notably, mutant microglia accumulate GTP‑bound RAB8A, which becomes hyperphosphorylated and mislocalized to RAB7-positive, LAMP1-negative vesicles. The GTPase-activating activity of the C9orf72/SMCR8 complex is essential for lysosomal repair. Our findings reveal that the C9orf72/SMCR8 complex coordinates RAB8A-ESCRT-mediated lysosomal repair to safeguard microglial homeostasis and limit neuroinflammation. - Source: PubMed
Publication date: 2026/05/29
Li ShanXu ShidongLi FengZhao QiruiZhang PenghuiGuan QinghuaSun XiangxiangBi JundongXiao HuTang YiyuliPeng ChengChen QingfengWang YonghuaYang Mei - Gain-of-function mutations in are a major cause of inherited Parkinson's disease. encodes a multidomain kinase, whose bidirectional interplay with Rab GTPases regulates critical cellular processes like lysosomal homeostasis. Certain Rabs, including Rab12 and Rab29, recruit LRRK2 to organelle membranes and stimulate its kinase activity; activated LRRK2 phosphorylates a subset of Rabs in their Switch-II motifs. Molecular basis governing selective Rab recognition by LRRK2 remains unclear. Here we structurally characterize LRRK2 interactions with representative Rab GTPases and identify three novel Rab-binding sites: site 4 for Rab8A/10, site 5 for Rab43, and site 6 for Rab5A, defining a total of six distinct binding sites that account for known LRRK2-interacting Rabs. Additionally, we elucidated the binding site of GABARAP, an ATG8 member that recruits LRRK2 to stressed lysosomes. Our findings provide a framework for therapeutic targeting of LRRK2 recruitment for Parkinson's. - Source: PubMed
Publication date: 2026/05/05
Zhu HanwenEade LiamAlessi Dario RSun Ji - Myocardial ischemia-reperfusion injury (MIRI) remains a critical complication associated with cardiopulmonary bypass (CPB). This study investigated whether p38 mitogen-activated protein kinase (p38MAPK) sustains myocardial glucose uptake by controlling glucose transporter-4 (GLUT4) expression and membrane translocation through distinct myocyte enhancer factor-2 (MEF2) isoforms. - Source: PubMed
Publication date: 2026/03/20
Gao WeilongZhang DanZhang BenfaSun PengCao YingYang SiyuanChen HongjinSong Yingnan - - Source: PubMed
Publication date: 2026/02/27
Schuelke SophieHaseeb SanaParmar Mayur S - Mutations in leucine-rich repeat kinase 2 (LRRK2) are among the most common genetic causes of Parkinson's disease (PD), yet substantial heterogeneity exists among pathogenic variants. How mutations in distinct functional domains of LRRK2 differentially perturb cellular homeostasis remains incompletely understood. Here, we compared two pathogenic LRRK2 mutations-G2019S in the kinase domain and I1371V in the GTPase domain-across multiple cellular models, including SH-SY5Y and U87 cells, and healthy human iPSC-derived floor plate cells. We demonstrate that the I1371V mutation induces markedly more severe cellular dysfunction than G2019S. I1371V-expressing cells exhibited elevated LRRK2 autophosphorylation at S1292 and robust hyperphosphorylation of Rab8A and Rab10, indicating enhanced downstream signaling. These alterations impaired sterol trafficking, leading to selective depletion of membrane cholesterol without changes in total cellular cholesterol. Consequently, I1371V cells displayed increased membrane fluidity, disrupted microdomain organization, altered membrane topology, reduced caveolin-1 expression, and impaired dopamine transporter surface expression and dopamine uptake. Lipidomic profiling further revealed a broad disruption of lipid homeostasis, including reductions in cholesteryl esters, sterols, sphingolipids, and glycerophospholipids, whereas G2019S cells showed comparatively modest changes. Pharmacological intervention revealed mutation-specific responses, with the non-selective LRRK2 modulator GW5074 outperforming the kinase-selective inhibitor MLi-2 in restoring Rab8A phosphorylation, membrane integrity, and dopaminergic function. Collectively, these findings identify membrane lipid dysregulation as a central cell biological mechanism in LRRK2-associated PD and underscore the importance of variant-specific therapeutic strategies. - Source: PubMed
Publication date: 2026/02/13
Singh KhushbooBanerjee RoonPotdar ChandrakantaShaw AnishaRakshith RakshithKamble NitishHolla VikramYadav RaviPal Pramod KumarDatta Indrani