Ask about this productRelated genes to: GABARAP antibody
- Gene:
- GABARAP NIH gene
- Name:
- GABA type A receptor-associated protein
- Previous symbol:
- -
- Synonyms:
- MM46, ATG8A
- Chromosome:
- 17p13.1
- Locus Type:
- gene with protein product
- Date approved:
- 1999-09-29
- Date modifiied:
- 2016-03-17
Related products to: GABARAP antibody
Related articles to: GABARAP antibody
- Macroautophagy/autophagy, a conserved intracellular catabolic pathway, removes deleterious cytosolic material to maintain homeostasis and survival. Upon autophagy induction, a unique double-membraned structure, the phagophore, forms and engulfs cytosolic material, the cargo, as it closes to become an autophagosome. Mammalian Atg8-family proteins (ATG8s) are ubiquitin-like proteins which are essential for engulfment of the cargo and membrane closure. ATG8s are recruited to the phagophore by ATG12-ATG5-ATG16L1, an E3-like ligase which is recruited by PtdIns3P-binding WIPI proteins. Covalent lipidation of the ATG8s to phosphatidylethanolamine by the E3 ligase occurs specifically on the phagophore membrane allowing recruitment of cytosolic cargo and cargo receptors, such as SQSTM1/p62. While ATG8-cargo receptor interactions are well established, how the ATG8s bind cargo and cargo receptors on the inner membrane of the phagophore has not been studied. To recapitulate these events, we use giant unilamellar vesicles (GUVs) and encapsulate protein machinery and cargo, generating a membrane platform to which ATG8 proteins can be recruited. Inside the GUVs we reconstituted WIPI2B-directed and cargo-directed ATG8 lipidation revealing distinct roles of WIPI2B and SQSTM1 in initiating ATG8 conjugation. We show that SQSTM1 and SQSTM1 droplets are recruited to the GUV inner membrane through interaction with membrane bound ATG8s. Through the development of a bead-based membrane deformation assay, we show redistribution and local enrichment of membrane-bound ATG8s occurs upon binding to SQSTM1 droplets. Our work demonstrates fundamental molecular mechanisms into phagophore-ATG8-cargo interactions providing novel model systems to investigate ATG8-cargo interactions on the inner phagophore membrane.:ATG: autophagy related; cDICE: continuous droplet interface crossing encapsulation; DOPE: 1,2-dioleoyl-sn-glycero-3-phosphoethanolamine; GABARAP: GABA type A receptor-associated protein; GUV: giant unilamellar vesicle; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; LIR: LC3-interacting region; LUV: large unilamellar vesicle; NBD: 7-nitrobenz-2-oxa-1,3-diazol-4-yl; PE: phosphatidylethanolamine; PtdIns: phosphatidylinositol; PtdIns3P: phosphatidylinositol-3-phosphate; PolyUb: K63-linked polyubiquitin; POPC: 1-palmitoyl-2-oleoyl-glycero-3-phosphocholine; POPE: 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine; Rh-PE: 18:1 Liss Rhod PE; SQSTM1/p62: sequestosome 1; WIPI2B: WD repeat domain, phosphoinositide interacting 2B. - Source: PubMed
Publication date: 2026/07/06
Zhang WenxinLitschel ThomasSchreiber AnneD'Antuono RoccoTooze Sharon A - The targeted, substrate-specific degradation of paternal mitochondria inside the zygote, known as post-fertilization sperm mitophagy, is a crucial and evolutionarily conserved early embryonic event. It ensures the exclusive maternal inheritance of the mitochondrial genome. Post-fertilization sperm mitophagy was initially thought to only be achieved via the ubiquitin-proteasome system. Until pro-autophagic receptor proteins such as SQSTM1, GABARAP, as well as the proteasome-interacting ubiquitinated protein dislocase VCP, were identified as contributors to the degradation of the sperm mitochondria early after mammalian fertilization. This synergy of proteasomal and autophagic pathways ensures a timely degradation of sperm mitochondria shortly after fertilization. The discovery of these autophagic receptors lead researchers to believe there might be other autophagic receptors and determinants necessary for proper post-fertilization sperm mitophagy. Based on the established inventory of proteins from mass spectrometry trials of boar spermatozoa exposed to porcine oocyte extracts in an intra-specific porcine cell-free system (CFS), five candidate mitophagy determinants were further investigated in this study, namely LACTB, PRDX3, PSMA8, TOMM34, and FUNDC1. These proteins of interest were studied and validated by using in vitro fertilization (IVF) protocols, cell imaging of spermatids, spermatozoa, oocytes and zygotes, protein interactome analysis, and the porcine CFS. The proteins PSMA8 and TOMM34 behaved in accordance with our proteomic study predictions. The PSMA8 labeling increased after exposure to CFS; in agreement with the classification PSMA8 was given from the mass spectrometry findings. TOMM34 underwent a visible decrease in labeling after exposure to CFS, which also agreed with its proteomic classification; this labeling persisted in IVF zygotes. Except for LACTB, the examined proteins showed mutual interactions as well as interactions with previously identified sperm mitophagy factors in the STRING interactome analysis. Results from this study validate the novel porcine CFS as a valuable tool for the exploration of early fertilization events at a molecular level. Future phenotyping and functional studies using porcine CFS will advance the understanding of mitochondrial inheritance and zygotic development and potentially shed light on the origins of certain mitochondrial diseases arising from the failure of post-fertilization sperm mitophagy. - Source: PubMed
Publication date: 2026/06/29
Jones AlexisZelenková NatálieMantle EricaGardner ChloeKlusáčková BarboraZuidema DalenSutovsky MiriamPostlerová PavlaZigo MichalSutovsky Peter - Crohns disease (CD) is characterized by persistent intestinal inflammation, immune dysregulation, and intestinal barrier dysfunction. Inflammasome-mediated pyroptosis is an innate immune mechanism increasingly implicated in inflammatory bowel disease (IBD); however, the upstream molecular signals associated with NLRP3-Caspase-1-GSDMD activation in CD remain insufficiently defined. Here, we explored whether the angiopoietin-1 (ANGPT1)-gamma-aminobutyric acid receptor-associated protein (GABARAP) axis is associated with CD-related pyroptotic signaling. - Source: PubMed
Publication date: 2026/06/10
Li YanchenHe JunyanGao PingFu ZeyangGuo YahuiGao HeLi ChenyangZhang Xiaolan - The cGAS-STING1 pathway is essential for innate immunity, while its functions beyond immune activation have emerged as a key research topic. Recent studies have revealed the non-canonical roles of this pathway in autophagy. However, whether it participates in organelle quality control through selective autophagy processes such as mitophagy remains largely unexplored. In our study, we identify the cGAS-STING1 pathway as an essential upstream regulator of PINK1-PRKN-dependent mitophagy. We demonstrate that upon mitochondrial damage, STING1 is recruited to damaged mitochondria in a process requiring PINK1- and VCP/p97-mediated degradation of outer mitochondrial membrane proteins. STING1 at damaged mitochondria then activates TBK1, which phosphorylates the mitophagy receptor OPTN at Ser177, enhancing its recruitment to damaged mitochondria and driving efficient mitophagy. Disruption of the STING1-TBK1-OPTN axis impairs mitophagy and shifts the cellular response from pro-survival mitophagy to apoptosis. Our findings therefore uncover a non-canonical, pro-survival function of the cGAS-STING1 pathway in mitophagy, extending its role beyond innate immunity to the regulation of selective autophagy and cell fate decisions.: BafA1: bafilomycin A1; cGAS: cyclic GMP‑AMP synthase; ER: endoplasmic reticulum; GABARAP: GABA type A receptor-associated protein; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MQC: mitochondrial quality control; mtDNA: mitochondrial DNA; NAC: N-Acetylcysteine; Nec-1: Necrostatin-1; OMM: outer mitochondrial membrane; OPTN: optineurin; PINK1: PTEN induced kinase 1; PRKN: parkin RBR E3 ubiquitin protein ligase; RIPK1: receptor interacting serine/threonine kinase 1; ROS: reactive oxygen species; STING1: stimulator of interferon response cGAMP interactor 1; TBK1: TANK binding kinase 1; TFEB: transcription factor EB; VCP/p97: valosin containing protein; Z-VAD-FMK: benzyloxycarbony (Cbz)-l-ValAla-Asp (OMe)-fluoromethylketone. - Source: PubMed
Publication date: 2026/06/18
Huang Ze-BoLin Jin-YiCheng Ling-JunTan Hayden Weng SiongShen Han-MingLu Guang - The GABA receptor-associated protein (GABARAP), a member of the autophagy-related protein 8 (ATG8) family, regulates autophagy and GABA receptor trafficking in mammals, yet its functional role in insects remains completely unexplored. The bean flower thrips, Megalurothrips usitatus, is a globally invasive pest whose control is increasingly challenged by widespread insecticide resistance. Understanding novel regulatory mechanisms in its nervous system, particularly those involving the insecticidal target GABA receptor (RDL), is therefore crucial. Spatiotemporal expression profiling revealed that GABARAP was predominantly expressed in the pseudopupa stage and in head tissues of M. usitatus. Its transcript level showed a significant positive correlation with the RDL expression across geographically distinct populations, and RNA interference (RNAi) GABARAP knockdown led to a concurrent reduction in RDL expression. Functional electrophysiology in Xenopus oocytes demonstrated that GABARAP and RDL co-expression enhanced the RDL sensitivity to GABA, lowering the EC₅₀ from 35.09 μM to 27.27 μM and increasing the maximal current response. Computational analyses confirmed the interaction: molecular docking predicted a stable, high-affinity GABARAP-RDL complex involving key residues (such as GABARAP GLU-101 and RDL ARG-411), and molecular dynamics simulations demonstrated its structural stability. MM/GBSA energy decomposition identified van der Waals forces as the primary drivers of complex formation. By providing the first evidence in insects that GABARAP directly binds to and potentiates the RDL receptor, this study establishes GABARAP as a positive regulator of inhibitory neurotransmission, thereby revealing a novel regulatory mechanism for insect GABA receptors. Therefore, the GABARAP-RDL interface thus represents a potential target for novel pest-control strategies. - Source: PubMed
Publication date: 2026/04/19
Jin HaifengLin YonghuiSingh SumitXie YuranJiang WayneLi FenWu Shaoying