The primate-specific Nedd4-1-NE localizes to late endosomes in response to amino acids to suppress autophagy
Ontology highlight
ABSTRACT:
INSTRUMENT(S): Q Exactive HF
ORGANISM(S): Homo Sapiens (ncbitaxon:9606)
SUBMITTER: 
Brian Raught
PROVIDER: MSV000093801 | MassIVE | Tue Jan 09 15:43:00 GMT 2024
SECONDARY ACCESSION(S): PXD048366
REPOSITORIES: MassIVE
Similar Datasets
Project description:Obese men have lower circulating testosterone than men with an optimal body mass index. Elevated fatty acids (FAs) caused by obesity have been reported to suppress the steroidogenesis of Leydig cells. Recent studies have demonstrated that autophagy regulates steroidogenesis in endocrine cells; however, few studies have investigated the molecular mechanisms of FA-impaired steroidogenesis. To study FA regulation in the steroidogenesis of Leydig cells, MA-10 cells were treated with an FA mixture and co-treated with 8-Br-cAMP to stimulate the steroidogenesis capacity. We showed that FAs led to cellular lipid accumulation and decreased steroidogenesis of MA-10 cells, and FA-suppressed steroidogenesis was largely recovered by P5 treatment but not by 22R-OHC treatment, suggesting the primary defect was the deficiency of CYP11A1. To examine the involvement of autophagy in the steroidogenesis of Leydig cells, we treated MA-10 cells with autophagy regulators, including rapamycin, bafilomycin, and chloroquine. Inhibition of late-stage autophagy including FA-upregulated Rubicon suppressed the steroidogenesis of MA-10 cells. More interestingly, Rubicon played a novel regulatory role in the steroidogenesis of MA-10 cells, independent of inhibitors of late-stage autophagy. Collectively, this study provides novel targets to investigate the interaction between FAs and steroidogenesis in steroidogenic cells.
| S-EPMC8206377 | biostudies-literature
Project description:Amino acids are required for activation of the mammalian target of rapamycin (mTOR) kinase which regulates protein translation, cell growth, and autophagy. Cell surface transporters that allow amino acids to enter the cell and signal to mTOR are unknown. We show that cellular uptake of L-glutamine and its subsequent rapid efflux in the presence of essential amino acids (EAA) is the rate-limiting step that activates mTOR. L-glutamine uptake is regulated by SLC1A5 and loss of SLC1A5 function inhibits cell growth and activates autophagy. The molecular basis for L-glutamine sensitivity is due to SLC7A5/SLC3A2, a bidirectional transporter that regulates the simultaneous efflux of L-glutamine out of cells and transport of L-leucine/EAA into cells. Certain tumor cell lines with high basal cellular levels of L-glutamine bypass the need for L-glutamine uptake and are primed for mTOR activation. Thus, L-glutamine flux regulates mTOR, translation and autophagy to coordinate cell growth and proliferation.
| S-EPMC3733119 | biostudies-literature
Project description:Autophagy delivers cytosolic components to lysosomes for their degradation. The delivery of autophagic cargo to late endosomes for complete or partial degradation has also been described. In this report we present evidence that distinct autophagic mechanisms control cytosolic protein delivery to late endosomes and identify a microautophagy-like process that delivers soluble cytosolic proteins to the vesicles of late endosomes/multivesicular bodies (MVBs). This microautophagy-like process has selectivity and is distinct from chaperone-mediated autophagy that occurs in lysosomes. Endosomal microautophagy occurs during MVB formation, relying on the ESCRT I and III systems for formation of the vesicles in which the cytosolic cargo is internalized. Protein cargo selection is mediated by the chaperone hsc70 and requires the cationic domain of hsc70 for electrostatic interactions with the endosomal membrane. Therefore, we propose that endosomal microautophagy shares molecular components with both the endocytic and autophagic pathways.
| S-EPMC3025279 | biostudies-literature
Project description:D-amino acids enrichment Raw sequence reads
| PRJNA745484 | ENA
Project description:In the upper respiratory epithelium, bitter and sweet taste receptors present in solitary chemosensory cells influence antimicrobial innate immune defense responses. Whereas activation of bitter taste receptors (T2Rs) stimulates surrounding epithelial cells to release antimicrobial peptides, activation of the sweet taste receptor (T1R) in the same cells inhibits this response. This mechanism is thought to control the magnitude of antimicrobial peptide release based on the sugar content of airway surface liquid. We hypothesized that d-amino acids, which are produced by various bacteria and activate T1R in taste receptor cells in the mouth, may also activate T1R in the airway. We showed that both the T1R2 and T1R3 subunits of the sweet taste receptor (T1R2/3) were present in the same chemosensory cells of primary human sinonasal epithelial cultures. Respiratory isolates of Staphylococcus species, but not Pseudomonas aeruginosa, produced at least two d-amino acids that activate the sweet taste receptor. In addition to inhibiting P. aeruginosa biofilm formation, d-amino acids derived from Staphylococcus inhibited T2R-mediated signaling and defensin secretion in sinonasal cells by activating T1R2/3. d-Amino acid-mediated activation of T1R2/3 also enhanced epithelial cell death during challenge with Staphylococcus aureus in the presence of the bitter receptor-activating compound denatonium benzoate. These data establish a potential mechanism for interkingdom signaling in the airway mediated by bacterial d-amino acids and the mammalian sweet taste receptor in airway chemosensory cells.
| S-EPMC5615852 | biostudies-literature
Project description:Data deposited contain results from proximity-dependent biotinylation LC-MS (BioID) experiments in which 786-O and RCC243 cells expressed PRMT1 protein fused to miniTurbo biotin carboxylase.
2024-05-01 | MSV000094655 | MassIVE
Project description:The endoplasmic reticulum (ER) is the largest organelle contacting virtually every other organelle for information exchange and control of processes such as transport, fusion, and fission. Here, we studied the role of the other organelles on ER network architecture in the cell periphery. We show that the co-migration of the ER with other organelles, called ER hitchhiking facilitated by late endosomes and lysosomes is a major mechanism controlling ER network architecture. When hitchhiking occurs, emerging ER structures may fuse with the existing ER tubules to alter the local ER architecture. This couples late endosomal/lysosomal positioning and mobility to ER network architecture. Conditions restricting late endosomal movement-including cell starvation-or the depletion of tether proteins that link the ER to late endosomes reduce ER dynamics and limit the complexity of the peripheral ER network architecture. This indicates that among many factors, the ER is controlled by late endosomal movement resulting in an alteration of the ER network architecture.
| S-EPMC7926257 | biostudies-literature
Project description:Data deposited contains results from proximity-labeling LC-MS experiment performed in T-REx Flp-In HEK293 cells stably expressing RPB9/POLR2I fused with the biotin carboxylase miniTurbo.
2024-03-13 | MSV000094316 | MassIVE
Project description:Semliki forest virus (SFV) is internalized by clathrin-mediated endocytosis, and transported via early endosomes to late endosomes and lysosomes. The intracellular pathway taken by individual fluorescently labeled SFV particles was followed using immunofluorescence in untransfected cells, and by video-enhanced, triple-color fluorescence microscopy in live cells transfected with GFP- and RFP-tagged Rab5, Rab7, Rab4, and Arf1. The viruses progressed from Rab5-positive early endosomes to a population of early endosomes (about 10% of total) that contained both Rab5 and Rab7. SFV were sequestered in the Rab7 domains, and they were sorted away from the early endosomes when these domains detached as separate transport carriers devoid of Rab5, Rab4, EEA1, Arf1, and transferrin. The process was independent of Arf1 and the acidic pH in early endosomes. Nocodazole treatment showed that the release of transport carriers was assisted by microtubules. Expression of constitutively inactive Rab7T22N resulted in accumulation of SFV in early endosomes. We concluded that Rab7 is recruited to early endosomes, where it forms distinct domains that mediate cargo sorting as well as the formation of late-endosome-targeted transport vesicles.
| S-EPMC1151600 | biostudies-literature
Project description:The clinical efficacy of a late evening snack (LES) is well documented in patients with cirrhosis, but its effect on survival remains unclear. This cohort study aimed to compare the overall survival between LES-treated patients and untreated patients. We conducted a retrospective cohort study to determine the effect of LES, which is defined as an oral intake of a branched-chain amino acids (BCAA)-enriched nutrient before bedtime, on survival in 523 patients with cirrhosis seen at a tertiary referral center in Japan from March 2004 to April 2019. The association between LES and all-cause mortality was evaluated using propensity score matching and inverse probability of treatment weighting analyses. The median age of the 523 participants was 66 years; 286 (55%) patients were men and 87 (17%) received LES therapy. Of the 231 propensity-matched patients, 20 (26%) LES-treated patients and 72 (47%) untreated patients died during a median follow-up of 2.0 years (interquartile range, 0.5-4.8). Propensity score matching analysis showed that the overall survival was significantly higher in LES-treated patients than in untreated patients (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.34-0.93). The survival benefit of LES therapy was most prominent in patients with Child-Pugh C cirrhosis (HR, 0.40; 95% CI, 0.20-0.81). Inverse probability of treatment weighting analysis also revealed that LES significantly improved the prognosis of patients with cirrhosis (HR, 0.57; 95% CI, 0.33-0.99). In this retrospective study of patients with cirrhosis, we found that nocturnal BCAA supplementation was associated with a significant reduction in the risk of death in patients with liver cirrhosis.
| S-EPMC7230335 | biostudies-literature