ArticleJournal of neurochemistry2008
Tissue-type plasminogen activator requires a co-receptor to enhance NMDA receptor function.
Article in Journal of neurochemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
61 citing papers in PubMed, 119 citations in OpenAlex.
- The Plasminogen Activation System in the Central Nervous System: Implications for Epilepsy and Neuropsychiatric Disorders.International journal of molecular sciences · 2025Review
- Modeling and correction of protein conformational disease in iPSC-derived neurons through personalized base editing.Molecular therapy. Nucleic acids · 2025Article
- Intracellular tPA-PAI-1 interaction determines VLDL assembly in hepatocytes.Science (New York, N.Y.) · 2023Article
- An antibody that targets cell-surface glucose-regulated protein-78 inhibits expression of inflammatory cytokines and plasminogen activator inhibitors by macrophages.Journal of cellular biochemistry · 2023Article
- Platelet-targeted thrombolysis for treatment of acute ischemic stroke.Blood advances · 2023Article
- Tissue-type plasminogen activator induces conditioned receptive field plasticity in the mouse auditory cortex.iScience · 2023Article
- Blood tissue Plasminogen Activator (tPA) of liver origin contributes to neurovascular coupling involving brain endothelial N-Methyl-D-Aspartate (NMDA) receptors.Fluids and barriers of the CNS · 2023Article
- Modulations of the neuronal trafficking of tissue-type plasminogen activator (tPA) influences glutamate release.Cell death & disease · 2023Article
- Low-density lipoprotein receptor-related protein-1 (LRP1) in the glial lineage modulates neuronal excitability.Frontiers in network physiology · 2023Review
- tPA-NMDAR Signaling Blockade Reduces the Incidence of Intracerebral Aneurysms.Translational stroke research · 2022Article
- Targeting NMDA Receptors at the Neurovascular Unit: Past and Future Treatments for Central Nervous System Diseases.International journal of molecular sciences · 2022Review
- Tissue Plasminogen Activator in Central Nervous System Physiology and Pathology: From Synaptic Plasticity to Alzheimer's Disease.Seminars in thrombosis and hemostasis · 2022Review
- Low-intensity blast induces acute glutamatergic hyperexcitability in mouse hippocampus leading to long-term learning deficits and altered expression of proteins involved in synaptic plasticity and serine protease inhibitors.Neurobiology of disease · 2022Article
- Two-Chains Tissue Plasminogen Activator Unifies Met and NMDA Receptor Signalling to Control Neuronal Survival.International journal of molecular sciences · 2021Article
- Plasminogen activator receptor assemblies in cell signaling, innate immunity, and inflammation.American journal of physiology. Cell physiology · 2021Review
- The Fibrinolytic System: Mysteries and Opportunities.HemaSphere · 2021Review
- Enzymatically Inactive Tissue-Type Plasminogen Activator Reverses Disease Progression in the Dextran Sulfate Sodium Mouse Model of Inflammatory Bowel Disease.The American journal of pathology · 2021Article
- Serine Proteases and Chemokines in Neurotrauma: New Targets for Immune Modulating Therapeutics in Spinal Cord Injury.Current neuropharmacology · 2021Review
- tPA Deficiency Underlies Neurovascular Coupling Dysfunction by Amyloid-β.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2020Article
- Tissue-Type Plasminogen Activator and Tenecteplase-Mediated Increase in Blood Brain Barrier Permeability Involves Cell Intrinsic Complement.Frontiers in neurology · 2020Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 3 countries.
Funding
Abstract
Glutamate is the main excitatory neurotransmitter of the CNS. Tissue-type plasminogen activator (tPA) is recognized as a modulator of glutamatergic neurotransmission. This attribute is exemplified by its ability to potentiate calcium signaling following activation of the glutamate-binding NMDA receptor (NMDAR). It has been hypothesized that tPA can directly cleave the NR1 subunit of the NMDAR and thereby potentiate NMDA-induced calcium influx. In contrast, here we show that this increase in NMDAR signaling requires tPA to be proteolytically active, but does not involve cleavage of the NR1 subunit or plasminogen. Rather, we demonstrate that enhancement of NMDAR function by tPA is mediated by a member of the low-density lipoprotein receptor (LDLR) family. Hence, this study proposes a novel functional relationship between tPA, the NMDAR, a LDLR and an unknown substrate which we suspect to be a serpin. Interestingly, whilst tPA alone failed to cleave NR1, cell-surface NMDARs did serve as an efficient and discrete proteolytic target for plasmin. Hence, plasmin and tPA can affect the NMDAR via distinct avenues. Altogether, we find that plasmin directly proteolyses the NMDAR whilst tPA functions as an indirect modulator of NMDA-induced events via LDLR engagement.
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Registered trials
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.