Ask about this productRelated genes to: ATG9A Blocking Peptide
- 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 Blocking Peptide
Related articles to: ATG9A Blocking Peptide
- 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 - Biological membranes provide a resilient framework for cellular structure and stability. Disrupting its integrity may result in irreparable damage, altering cellular homeostasis and ultimately leading to cell death. ATG9A, a transmembrane protein, has recently been implicated in plasma membrane repair. However, its role in the process and the mechanism by which it is targeted to the plasma membrane upon damage are unclear. We show here that glycosylation of ATG9A is essential for its membrane repair activity. This has been corroborated by using different mutant cells that are defective in their ability to process proteoglycan in the Golgi complex. Specifically, sialylation of the sugar moiety appears vital for plasma membrane repair activity. Additionally, we provide evidence indicating that ATG9A is targeted to the plasma membrane through interaction with the endosomal sorting complex required for transport complex. Finally, we found that ATG9A lipid scramblase activity and the lipid transfer protein VPS13A are needed for efficient membrane repair. - Source: PubMed
Publication date: 2026/04/27
Muskat Natali HNevo-Yassaf InbarChaurasia MadhuriReiss ShaniGoliand InnaKupervaser MeitalAddadi YosephLevin YishaiFraiberg MilanaElazar Zvulun - The small GTPase RAB1 is essential for life. A knockout of RAB1 is not only embryonically lethal, but even triggers cell death in a cultured cell line, underscoring its importance for cellular homeostasis. Previous work has shown that RAB1 plays a key role in protein and membrane trafficking as a player in the ER-to-Golgi trafficking pathway. Here, RAB1 has been shown to interact with COPII vesicles that have left the ER and are arriving at the Golgi. In addition, RAB1 is an essential part of autophagy initiation, where loss of RAB1 leads to defects very early in the pathway. To complicate matters further, there is a non-trivial overlap in phenotype between a Golgi trafficking defect and an autophagy initiation problem, as ATG9A vesicle trafficking and the general importance of the Golgi in autophagy illustrates. Given these hurdles, how would one get a handle on the molecular mechanism of RAB1? In this Punctum, I discuss our recent mapping of a new RAB1 interactome that provides fresh insights into its multifaceted functions. - Source: PubMed
Publication date: 2026/04/21
van Vliet Alexander R - Autophagy involves the rapid growth of phagophores through membrane addition. This growth is triggered by vesicles containing the Atg9A protein. However, Atg9A is not incorporated into mature autophagosomes. We now demonstrate that Dynamin-2 (Dnm2) colocalizes with the BAR domain protein Endophilin-B1 (EndoB1/Bif-1/SH3GLB1) and other autophagy proteins when autophagy is induced. Our data suggest that Atg9A is retrieved from phagophores via fission, with Dnm2 acting as the membrane scission protein. Blocking Atg9A recycling, either by mutating Dnm2, using RNA interference, or applying chemical inhibitors, results in Atg9A remaining in autophagosomes and being degraded during autophagy. Overall, these findings provide new insights into the roles of membrane-scission proteins in autophagy. - Source: PubMed
Publication date: 2026/03/13
Caliri AndrewRiera Alejandro MartorellSaha AkashKolitsida PanagiotaMartinez Cinta IriondoItskanov SamuelSteffen JanosKoehler Carla Mvan der Bliek Alexander M - Prion diseases are chronic, transmissible, and neurodegenerative disorders that affect both humans and other mammals. Mitophagy is essential for maintaining mitochondrial homeostasis and normal neuronal function. Our previous research show that the PINK1-Parkin-dependent mitophagy pathway is impaired in the PrP induced prion disease model, yet the underlying downstream mechanisms remain elusive. We report that impaired phosphorylation of ubiquitin at Ser65 diminishes OPTN recruitment to mitochondria, thereby influence mitochondrial translocation of TBK1 and ATG9A, consequently suppresses TBK1 autophosphorylation that depends on the OPTN-ATG9A interaction. As a result, reduction of OPTN phosphorylation dependent on TBK1 inhibits autophagosome formation and ultimately leads to defective mitophagy. Importantly, overexpression of OPTN rescued the mitophagy impairment induced by PrP and partially restoring mitochondrial morphology and function. Our findings identify OPTN as a critical node, proposing its therapeutic targeting as a strategy to counteract prion disease progression. - Source: PubMed
Publication date: 2026/04/07
Wang JingjingWen PeiSun ZhixinGou FengtingFan QingHe YuhengZhao DemingYang Lifeng