TBC1D23 mediates Golgi-specific LKB1 signaling
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Da Jia
PROVIDER: PXD040801 | iProX | Mon Mar 13 00:00:00 GMT 2023
REPOSITORIES: iProX
Publications
TBC1D23 mediates Golgi-specific LKB1 signaling.
Tu Yingfeng Y Yang Qin Q Tang Min M Gao Li L Wang Yuanhao Y Wang Jiuqiang J Liu Zhe Z Li Xiaoyu X Mao Lejiao L Jia Rui Zhen RZ Wang Yuan Y Tang Tie-Shan TS Xu Pinglong P Liu Yan Y Dai Lunzhi L Jia Da D
Nature communications 20240227 1
Liver kinase B1 (LKB1), an evolutionarily conserved serine/threonine kinase, is a master regulator of the AMPK subfamily and controls cellular events such as polarity, proliferation, and energy homeostasis. Functions and mechanisms of the LKB1-AMPK axis at specific subcellular compartments, such as lysosome and mitochondria, have been established. AMPK is known to be activated at the Golgi; however, functions and regulatory mechanisms of the LKB1-AMPK axis at the Golgi apparatus remain elusive. ...[more]
Similar Datasets
Project description:We explore the transcriptional response of mammalian cells undergoing various insults to Golgi homeostasis. HEK293 cells (Flp-In T-REx 293 cells) stably containing a doxycycline-inducible Golgi-localized HaloTag2 construct (GA-HT2) were treated with the ionophore nigericin, the glycosylation inhibitor xyloside, or were induced by doxycycline and treated with the hydrophobic tag HyT36 to induce destabilization of GA-HT2. We found that while nigericin and xyloside induce global transcriptional changes, destabilization of GA-HT2 induces a Golgi-specific response.
2018-06-21 | GSE99490 | GEO
Project description:The Golgi is a membrane-bound organelle that is essential for protein and lipid biosynthesis. It represents a central trafficking hub that sorts proteins and lipids to various destinations or for secretion from the cell. The Golgi has emerged as a docking platform for cellular signaling pathways including LRRK2 kinase whose deregulation leads to Parkinson disease. Golgi dysfunction is associated with a broad spectrum of diseases including cancer, neurodegeneration, and cardiovascular diseases. To allow the study of the Golgi at high resolution, we report a rapid Golgi immunoprecipitation technique (Golgi-IP) to isolate intact Golgi mini-stacks for subsequent analysis of their content. By fusing the Golgi-resident protein TMEM115 to three tandem HA epitopes (GolgiTAG), we purified the Golgi using Golgi-IP with minimal contamination from other compartments. We then established an analysis pipeline using liquid chromatography coupled with mass spectrometry to characterize the human Golgi proteome, metabolome, and lipidome. Subcellular proteomics confirmed known Golgi proteins and identified proteins not previously associated with the Golgi. Metabolite profiling established the human Golgi metabolome and revealed the enrichment of uridine-diphosphate (UDP) sugars and their derivatives, which is consistent with their roles in protein and lipid glycosylation. Furthermore, targeted metabolomics validated SLC35A2 as the subcellular transporter for UDP-hexose. Finally, lipidomics analysis showed that phospholipids including phosphatidylcholine, phosphatidylinositol, and phosphatidylserine are the most abundant Golgi lipids and that glycosphingolipids are enriched in this compartment. Altogether, our work establishes a comprehensive molecular map of the human Golgi and provides a powerful method to study the Golgi with high precision in health and disease.
2023-06-27 | MTBLS6511 | MetaboLights
Project description:The process of aging is associated with disturbed mineral homeostasis, such as zinc deficiency. Simultaneously, cellular response to external stimuli, including receptor signaling and DNA repair response diminishes, and epigenetic dysregulation occurs. The Golgi apparatus plays various roles in the cell; however, the effect of aging on the morphology and function of the Golgi apparatus and the impact of Golgi senescence in cellular activity remains unknown. In the present study, we found that Golgi stress is associated with senescent cell irresponsiveness to external stimuli. The senescent Golgi was associated with a disassembled microtubule network in the Golgi and perinuclear areas. These effects could be reproduced by disruption of the Golgi-associated microtubules or zinc depletion. To clarify the importance of Golgi-zinc homeostasis in more detail, the implications of the Golgi-zinc transporter ZIP13 were analyzed; Zip13-deficient mice Golgi exhibited morphology similar to that of senescent Golgi. Additionally, fibroblasts from Zip13-deficient mice showed dysregulation of DNA repair and cellular acetylation with downregulated nuclear translocation of p300, HDAC1/2, and p53 proteins, which are reminiscent characteristics of senescent cells. Our findings demonstrate the underlying reason for senescent cell irresponsiveness to various stimuli and highlight the importance of a zinc-rich diet during aging.
2024-08-26 | GSE235450 | GEO
Project description:The Golgi plays an essential role in protein and lipid glycosylation. Golgi dysfunction is associated with a variety of diseases including cancer, neurodegeneration and cardiovascular disease. We developed a powerful immunoprecipitation technique to isolate the Golgi by tagging TMEM115. Golgi-immunoprecipitation enriched protein markers specific for the organelle with minimal contamination from other subcellular compartments. Using this technique, we characterised the Golgi proteome, metabolome and lipidome. Proteomics analysis confirmed capture of known Golgi proteins and identified additional candidates enriched in the organelle. Metabolomics analysis revealed selective enrichment of uridine-diphosphate (UDP) sugars and their derivatives and validated SLC35A2 as the subcellular transporter for UDP-hexose. Lastly, lipidomics analysis showed that phospholipids including phosphatidylcholine, phosphatidylinositol and phosphatidylserine are the top enriched Golgi lipids. Our Golgi-IP workflow provides a paradigm for multimodal analysis of Golgi molecular content with enhanced subcellular precision.
2023-04-24 | PXD038046 | Pride
Project description:The intracellular transport system is an evolutionally conserved, essential, and highly regulated network of organelles and small transport carriers that traffic protein and lipid cargoes within the cell. The Conserved Oligomeric Golgi (COG) complex is the major Golgi Multisubunit Tethering Complex. Its key function is orchestration of SNARE mediated fusion of cargo carriers at the Golgi. We hypothesized the depletion of the major Golgi SNAREs GS28 (GOSR1) and GS15 (BET1L) due to COG malfunction is the major contributor to COG-related glycosylation defects. To test this, we created single, double and triple knockouts (KO) of Golgi SNAREs in HEK293T cells and analyzed the resulting mutants using a comprehensive set of biochemical, mass-spectrometry (MS) and microscopy approaches. Deletion of GS28 significantly affected GS15, but not the other two partners, STX5 and YKT6. Surprisingly, our analysis revealed that COG dysfunction is more deleterious for Golgi function than disrupting the canonical Golgi SNARE complex indicating the existence of an adaption mechanism. Indeed, quantitative mass-spectrometry analysis of STX5-interacting proteins revealed unexpected flexibility in Golgi SNARE pairing in mammalian cells. We uncovered two novel non-canonical Golgi SNARE complexes – STX5/SNAP29/VAMP7 and STX5/VTI1B/GS15/YKT6 which were increased in GS28 KO cells. Upon GS28 deletion, SNAP29 remarkably localized to the Golgi. Merely mislocalizing STX5 from Golgi abolished the SNARE substitution causing dramatic glycosylation defects. Our data points to the remarkable plasticity in the intra-Golgi membrane fusion machinery and places STX5 as the only essential Golgi Qa-SNARE.
2023-06-26 | PXD036741 | Pride
Project description:Golgi-ER Axis Regulates Anti-Tumor T Cell Immunotherapeutic Response
| PRJNA1048442 | ENA
Project description:Golgi degradation by selective autophagy (Golgiphagy) requires receptors to direct Golgi fragments into phagophores for sequestration within autophagosomes, followed by lysosomal degradation. Here, we show that the Golgi transmembrane protein TM9SF3 is a receptor essential for Golgiphagy under nutrient stress and multiple Golgi stress conditions. TM9SF3 binds all six mammalian ATG8 proteins through its N-terminal LC3-interacting regions. TM9SF3 knockout blocks nutrient stress-induced Golgi fragmentation and reduces the targeting of Golgi fragments to autophagosomes, resulting in decreased Golgi protein degradation. Beyond nutrient stress, TM9SF3 is required for Golgiphagy induced by monensin and brefeldin A treatments, and disruptions in intra-Golgi protein glycosylation. Knockout of TM9SF3 and mutations in its LIRs both compromise protein glycosylation, whereas TM9SF3 overexpression promotes degradation of incompletely glycosylated proteins. Further, we show that TM9SF3 is required for breast cancer cell proliferation, and high TM9SF3 levels are associated with poor prognosis, implicating its function in breast cancer pathology.
2025-03-18 | PXD062007 |
Project description:Loss of function of FAM177A1, a Golgi complex localized protein, causes a novel neurodevelopmental disorder
| PRJNA1044115 | ENA
Project description:The cumulative role of cellular organelle’s in shaping the life and function of a cell has been long acknowledged. While each organelle plays a specific role in the growth and development of T cells, numerous studies have thus far focused on targeting mitochondria, endoplasmic reticulum, or lysosome related pathways to improve anti-tumor T cell immune response. Here we highlight the tumor microenvironment (TME) mediated disruption of Golgi architecture and function, termed Golgi stress, contributes to altered redox signaling and affects cell survival. Importantly, the decreased expression if GM130, a marker of Golgi stress and indicating the disruption of Golgi architecture, was reverted upon treatment with hydrogen sulphide (H2S) donor GYY4137, or over expressing cystathionine β-synthase (Cbs), an enzyme involved in biosynthesis of endogenous H2S. Activation and expansion of tumor reactive TCR or chimeric antigen receptor bearing T cells expanded with exogenous H2S promoted stemness, antioxidant capacity and exhibited an increase effector cytokine secretion that correlated to increased protein translation. In in vivo models of melanoma and lymphoma, anti-tumor T cells conditioned ex vivo with exogenous H2S or overexpressing Cbs demonstrated superior tumor control upon ACT. Further, sorting anti- tumor T cells based on Golgi structure and abundance resulted in identification of a Golgihi subset of T cells with a unique metabolic signature, superior fitness, and enhanced anti-tumor capacity. These data suggest that H2S can be used an immunomodulatory agent to enhance the efficacy of ACT, and that the structure and function of the Golgi apparatus is an important feature of T cells that determines their anti-tumor capacity.
2024-11-20 | GSE249287 | GEO
Project description:FERONIA (FER) is a plasma membrane-localized receptor-like kinase (RLK) that belongs to the Catharantus roseus RLK1-like (CrRLK1L) subfamily. FER serves as a potential cell wall sensor that regulates multiple phytohormones, including ABA, JA, SA, BR, auxin, and ethyl, but the underlying regulatory mechanisms are still largely unknown. To further understand how FER regulates downstream signaling pathway, we performed FER-interacting proteins via immunoprecipitation-mass spectrometry (IP-MS) assay generated from FER-GFP transgenic plants.
2024-09-14 | PXD047596 | Pride