ATG9A siRNA_Lentivectors
- Known as:
- ATG9A siRNA_Lentivectors
- Catalog number:
- i001537c
- Product Quantity:
- 500ng
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ATG9A siRNA_Lentivectors
Related genes to: ATG9A siRNA_Lentivectors
- Gene:
- ATG9A NIH gene
- Name:
- autophagy related 9A
- Previous symbol:
- APG9L1
- Synonyms:
- FLJ22169
- Chromosome:
- 2q35
- Locus Type:
- gene with protein product
- Date approved:
- 2004-11-24
- Date modifiied:
- 2015-09-11
Related products to: ATG9A siRNA_Lentivectors
Related articles to: ATG9A siRNA_Lentivectors
- : Autophagy is an evolutionarily conserved intracellular degradation mechanism that is regulated by a set of autophagy-related (ATG) proteins. The only transmembrane protein among ATGs is the lipid scramblase ATG9, which exists in the form of two paralogs, ATG9A and ATG9B, in humans and other vertebrates. : Here, we analyzed human and murine skin transcriptome and proteome datasets for the expression of ATG9 paralogs and performed comparative genomics to determine their conservation during the evolution of amniotes (mammals and sauropsids). : The expression of , but not of , is enriched in differentiated epidermal keratinocytes and in skin appendages of humans and mice. In contrast to the conservation of in all major clades of amniotes, has been lost in at least three phylogenetic lineages. Cetaceans, which have unique skin adaptations to aquatic life, harbor mutations that disrupt the open reading frame of . Many or all species of turtles () and crocodilians () have entirely lost the gene. : has undergone independent pseudogenization or gene loss in different subgroups of amniotes. In mammalian species that have retained the gene, its expression pattern indicates functions of in the skin and skin appendages. - Source: PubMed
Publication date: 2026/06/09
Sukseree SupawadeeEckhart Leopold - Lens fibers undergo organelle degradation during lens terminal differentiation. Defects in organelle degradation of lens fibers lead to congenital cataract. As a member of heat shock factor family, HSF4 governs lens development by regulating the expression of key factors. HSF4 transcriptionally regulates ATG9a to induce organelle degradation via the autophagic pathway during lens terminal differentiation. HSF4 is also required for the organelle membrane translocation of phospholipases PLAATs, which were suggested to promote organelle degradation independent of autophagy in lens fibers. However, the detailed mechanism how HSF4 induces organelle degradation in lens fibers still remains unknown. In this study, we found that lipid peroxidation was extensively suppressed in HSF4 mouse lens fibers. HSF4 likely transcriptionally regulated the expression of lipoxygenase ALOX15 in lens. ALOX15 is uniquely expressed in lens fibers and colocalized with organelles in differentiating lens fibers. Knockout of ALOX15 had little effect on the organelle degradation in lens fibers. Unlike the total inhibition in HSF4 lens fibers, lipid peroxidation was only partially disturbed in ALOX15 lens fibers, possibly due to the compensatory role of ALOX12. Our findings demonstrate that HSF4 promotes lipid peroxidation by transcriptionally regulating ALOX15 expression in lens fibers, thus may contribute to the organelle degradation during lens OFZ formation. These findings expand our understanding of the molecular mechanisms underlying lens terminal differentiation. - Source: PubMed
Publication date: 2026/06/24
Zhang ShaoliWang YinanJiang NingLi XiaoyuHan LuyuanChen SiyuXie TongxinYan HongxinLi JunjieHu YanzhongMu HongmeiZhang JingCui Xiukun - Loss-of-function mutations in the genes encoding PINK1 and PRKN result in early-onset Parkinson disease (EOPD). Together, the encoded enzymes direct a neuroprotective pathway that ensures the elimination of damaged mitochondria via autophagy. We performed a genome-wide high-content imaging miRNA screen for inhibitors of the PINK1-PRKN pathway and identified all three members of the miRNA family 29 (miR-29). RNA sequencing revealed target genes regulated by miR-29 and identified ATG9A as a candidate gene. SiRNA-mediated ATG9A silencing phenocopied the effects of miR-29 and suppressed the initiation of PINK1-PRKN-mediated mitophagy. In addition, expression of ATG9A was able to rescue the effects of miR-29a, suggesting that ATG9A is primarily responsible for the inhibitory effect of miR-29. In an EOPD patient cohort, we further discovered two rare, potentially deleterious, missense variants (p.R631W and p.S828L) and tested them experimentally in cells. Strikingly, neither EOPD variant was able to rescue the phenotype suggesting they both act as loss-of-function mutations and might contribute to the etiology of disease. Together, our study validates miR-29 and its target gene ATG9A as novel regulators of PINK1-PRKN signaling. It further serves as proof-of-concept with the identification of novel, potentially disease-relevant EOPD variants specifically in mitophagy-regulating genes. The nomination of biological pathways is important for the stratification and treatment of patients that suffer from devastating diseases, such as EOPD. - Source: PubMed
Publication date: 2026/04/30
Markham Briana NRamnarine ChloeKim SongeunGrever William ESoto-Beasley Alexandra IHeckman Michael GRen YingxueOsborne Andrew CKehili MohammedBhagwate Aditya VLiu YuanhangWang ChenKim JungsuWszolek Zbigniew KRoss Owen ASpringer WolfdieterFiesel Fabienne C - WNT2B is canonically characterized as a secreted WNT-family ligand, which is transported to the extracellular space via the endoplasmic reticulum (ER)-Golgi pathway and binds to cell surface FZDs (frizzled class receptors) to trigger downstream signaling cascades. Here, we identify a previously unrecognized non-secretory intracellular function of WNT2B in impairing endosomal trafficking to inhibit macroautophagy/autophagy, as well as a non-canonical LC3B-II-dependent autophagic secretion mechanism for WNT2B. Specifically, the non-secretory intracellular pool of WNT2B via its conserved middle domain (MD) binds to the spectrin repeat domain (SRD) of WASHC5, competitively displacing WASHC1 and thereby disrupting WASH complex assembly and inhibiting WASHC1-mediated actin polymerization on early endosomes. This disruption impairs endosomal cargo trafficking, including the core autophagy protein ATG9A, leading to defective autophagy initiation and subsequent accumulation of pro-inflammatory and pro-fibrotic factors in fibroblasts. We validated this mechanism in vivo using a TNBS-induced mouse model of chronic colitis. Fibroblast-specific deletion restores autophagy, reduces pro-inflammatory cytokine secretion, and ameliorates intestinal fibrosis. Consistently, in Crohn disease (CD) patient tissues, elevated WNT2B in fibrotic regions negatively correlates with autophagy activity, and positively correlates with pro-fibrotic phenotypes, and clinical disease severity. Moreover, we identify a novel LC3B-II-dependent autophagic secretion pathway for WNT2B, which is distinct from the conventional ER-to-Golgi-dependent protein secretion. Collectively, our study delineates a novel non-canonical WNT2B-WASH complex-ATG9A regulatory axis through which WNT2B impairs endosomal trafficking and disrupts autophagy, ultimately amplifying inflammation and fibrosis. This study suggests that WNT2B may serve as a promising therapeutic target for CD and autophagy-associated fibrotic disorders.: 3-MA: 3-methyladenine; AAV: adeno-associated virus; ACTA2: actin alpha 2, smooth muscle; ARPC2: actin related protein 2/3 complex subunit 2; ATG: autophagy related; CCN3: cellular communication network factor 3; CD: Crohn disease; CK666: 2-fluoro-N-[2-(2-methyl-1H-indol-3-yl)ethyl]benzamide; COL1A1: collagen type I alpha 1 chain; Co-IP: co-immunoprecipitation; CTNNB1: catenin beta 1; DBcAMP: dibutyryl cyclic adenosine monophosphate; DPT: dermatopontin; EEA1: early endosome antigen 1; EGFR: epidermal growth factor receptor; ELISA: enzyme-linked immunosorbent assay; ER: endoplasmic reticulum; ESCRT: endosomal sorting complexes required for transport; EV: extracellular vesicle; FRAP: fluorescence recovery after photobleaching; FL: full length; FZD: frizzled class receptor; GST: glutathione S-transferase; HIF: human intestinal fibroblast; HMGB1: high mobility group box 1; IKBKB: inhibitor of nuclear factor kappa B kinase subunit beta; IL6: interleukin 6; LDELS: LC3-dependent EV loading and secretion; LPS: lipopolysaccharide; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MD: middle domain; MEFs: mouse embryonic fibroblasts; MTOR: mechanistic target of rapamycin kinase; MVB: multivesicular body; NFKB: nuclear factor kappa B; NFKBIA: NFKB inhibitor alpha; PDCD6IP: programmed cell death 6 interacting protein; PLA: proximity ligation assay; RELA/p65: RELA proto-oncogene, NF-kB subunit; SAFB: scaffold attachment factor B; SES-CD: Simple Endoscopic Score for Crohn disease; SIM: super-resolution structured illumination microscopy; SMAD3: SMAD family member 3; SQSTM1/p62: sequestosome 1; SRD: spectrin repeat domain; TEM: transmission electron microscopy; TFRC: transferrin receptor; TGFB1: transforming growth factor beta 1; TGOLN2: trans-golgi network protein 2; TNBS: 2,4,6-trinitrobenzenesulfonic acid; TNF: tumor necrosis factor; VCA: Verprolin homology, Central and Acidic; WASHC: WASH complex subunit; WLS: Wnt ligand secretion mediator; WCL: whole cell lysates; WNT: Wnt family member; WT, wild type. - Source: PubMed
Publication date: 2026/06/03
Liu DanqiongCheng YanlingHuang ChuxiangXie KangJie JiananZhang QingqingLan LinChen PeiyuXie JingWang HongliRen LuLi HuiwenGeng LanlanGong SitangZhu YunCheng Yang - Biallelic loss-of-function variants in the adaptor protein complex 4 (AP-4) disrupt trafficking of transmembrane proteins at the trans-Golgi network, including the autophagy-related protein 9A (ATG9A), leading to childhood-onset hereditary spastic paraplegia (AP-4-HSP). AP-4-HSP is characterized by features of both a neurodevelopmental and degenerative neurological disease. To investigate the molecular mechanisms underlying AP-4-HSP and identify potential therapeutic targets, we conducted an arrayed CRISPR/Cas9 loss-of-function screen of 8,478 genes, targeting the 'druggable genome', in a human neuronal model of AP-4 deficiency. Through this phenotypic screen and subsequent experiments, key modulators of ATG9A trafficking were identified, and complementary pathway analyses provided insights into the regulatory landscape of ATG9A transport. Knockdown of ANPEP and NPM1 enhanced ATG9A availability outside the trans-Golgi network, suggesting they regulate ATG9A localization. These findings deepen our understanding of ATG9A trafficking in the context of AP-4 deficiency and offer a framework for the development of targeted interventions for AP-4-HSP. - Source: PubMed
Publication date: 2026/05/19
Ziegler MarvinGünter CedricAlecu Julian EXue XutongKim Hyo-MinSaffari AfshinDavies Alexandra KSahin MustafaEbrahimi-Fakhari Darius