ArticleThe EMBO journal1999
Loss of a prolyl oligopeptidase confers resistance to lithium by elevation of inositol (1,4,5) trisphosphate.
Article in The EMBO journal, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 171 citations in OpenAlex.
- Review
- The inositol pyrophosphate metabolism of Dictyostelium discoideum does not regulate inorganic polyphosphate (polyP) synthesis.Advances in biological regulation · 2022Article
- Dictyostelium discoideum: An Alternative Nonanimal Model for Developmental Toxicity Testing.Toxicological sciences : an official journal of the Society of Toxicology · 2021Article
- Article
- Inositol triphosphate-triggered calcium release blocks lipid exchange at endoplasmic reticulum-Golgi contact sites.Nature communications · 2021Article
- Structure-activity mapping of ARHGAP36 reveals regulatory roles for its GAP homology and C-terminal domains.PloS one · 2021Article
- UsingFrontiers in cell and developmental biology · 2021Review
- The Thyrotropin-Releasing Hormone-Degrading Ectoenzyme, a Therapeutic Target?Frontiers in pharmacology · 2020Review
- Gamma secretase orthologs are required for lysosomal activity and autophagic degradation inAutophagy · 2019Article
- Subcellular Localization of Prolyl Endopeptidase During the First Wave of Rat Spermatogenesis and in Rat and Human Sperm.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2019Article
- Diacylglycerol kinase (DGKA) regulates the effect of the epilepsy and bipolar disorder treatment valproic acid inDisease models & mechanisms · 2018Article
- The MSDIN family in amanitin-producing mushrooms and evolution of the prolyl oligopeptidase genes.IMA fungus · 2018Article
- Curcumin and derivatives function through protein phosphatase 2A and presenilin orthologues inDisease models & mechanisms · 2018Article
- Phosphoproteomics reveals that glycogen synthase kinase-3 phosphorylates multiple splicing factors and is associated with alternative splicing.The Journal of biological chemistry · 2017Article
- NDE1 and NDEL1 from genes to (mal)functions: parallel but distinct roles impacting on neurodevelopmental disorders and psychiatric illness.Cellular and molecular life sciences : CMLS · 2017Review
- Mechanism of Action of Prolyl Oligopeptidase (PREP) in Degenerative Brain Diseases: Has Peptidase Activity Only a Modulatory Role on the Interactions of PREP with Proteins?Frontiers in aging neuroscience · 2017Article
- Article
- Functional drug screening reveals anticonvulsants as enhancers of mTOR-independent autophagic killing of Mycobacterium tuberculosis through inositol depletion.EMBO molecular medicine · 2015Article
- Hypothalamic prolyl endopeptidase (PREP) regulates pancreatic insulin and glucagon secretion in mice.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- An ancestral non-proteolytic role for presenilin proteins in multicellular development of the social amoeba Dictyostelium discoideum.Journal of cell science · 2014Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The therapeutic properties of lithium ions (Li+) are well known; however, the mechanism of their action remains unclear. To investigate this problem, we have isolated Li+-resistant mutants from Dictyostelium. Here, we describe the analysis of one of these mutants. This mutant lacks the Dictyostelium prolyl oligopeptidase gene (dpoA). We have examined the relationship between dpoA and the two major biological targets of lithium: glycogen synthase kinase 3 (GSK-3) and signal transduction via inositol (1,4,5) trisphosphate (IP3). We find no evidence for an interaction with GSK-3, but instead find that loss of dpoA causes an increased concentration of IP3. The same increase in IP3 is induced in wild-type cells by a prolyl oligopeptidase (POase) inhibitor. IP3 concentrations increase via an unconventional mechanism that involves enhanced dephosphorylation of inositol (1,3,4,5,6) pentakisphosphate. Loss of DpoA activity therefore counteracts the reduction in IP3 concentration caused by Li+ treatment. Abnormal POase activity is associated with both unipolar and bipolar depression; however, the function of POase in these conditions is unclear. Our results offer a novel mechanism that links POase activity to IP3 signalling and provides further clues for the action of Li+ in the treatment of depression.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.