ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2012
Glutamate controls tPA recycling by astrocytes, which in turn influences glutamatergic signals.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 70 citations in OpenAlex.
- Tissue Plasminogen Activator as an Approved Strategy for Ischemic Stroke: A Review of tPA's Structure, Mechanism of Action and the Novel Targeting Methods.Journal of molecular neuroscience : MN · 2025Review
- Neuronal conversion of single-chain tissue-type plasminogen activator into its two-chain form: implications in neurodevelopment, learning, and memory.Cell death & disease · 2025Article
- Tissue-type plasminogen activator expression by endothelial cells and oligodendrocytes is required for proper CNS myelination.Acta neuropathologica communications · 2025Article
- Spatiotemporal perturbations of the plasminogen activation system in a rat model of acute organophosphate intoxication.Acta neuropathologica communications · 2025Article
- 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
- Astrocytes in fragile X syndrome.Frontiers in cellular neuroscience · 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
- PAI-1 production by reactive astrocytes drives tissue dysfibrinolysis in multiple sclerosis models.Cellular and molecular life sciences : CMLS · 2022Article
- Roles of the tissue-type plasminogen activator in immune response.Cellular immunology · 2022Review
- Non-Cell-Autonomous Factors Implicated in Parvalbumin Interneuron Maturation and Critical Periods.Frontiers in neural circuits · 2022Review
- Plasminogen Activators in Neurovascular and Neurodegenerative Disorders.International journal of molecular sciences · 2021Review
- Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) as a Novel Regulator of Early Astroglial Differentiation.Frontiers in cellular neuroscience · 2021Article
- Circulating tPA contributes to neurovascular coupling by a mechanism involving the endothelial NMDA receptors.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2020Article
- Glutamate controls vessel-associated migration of GABA interneurons from the pial migratory route via NMDA receptors and endothelial protease activation.Cellular and molecular life sciences : CMLS · 2020Article
- Deletion of LRP1 From Astrocytes Modifies Neuronal Network Activity in anFrontiers in cellular neuroscience · 2020Article
- Low-Density Lipoprotein Receptor-Related Protein 1 (LRP1) Is a Negative Regulator of Oligodendrocyte Progenitor Cell Differentiation in the Adult Mouse Brain.Frontiers in cell and developmental biology · 2020Article
- Fibrinolysis protease receptors promote activation of astrocytes to express pro-inflammatory cytokines.Journal of neuroinflammation · 2019Article
- Increased expression of plasminogen activator inhibitor-1 (PAI-1) is associated with depression and depressive phenotype in C57Bl/6J mice.Experimental brain research · 2019Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tissue-type plasminogen activator (tPA) regulates physiological processes in the brain, such as learning and memory, and plays a critical role in neuronal survival and neuroinflammation in pathological conditions. Here we demonstrate, by combining mouse in vitro and in vivo data, that tPA is an important element of the cross talk between neurons and astrocytes. The data show that tPA released by neurons is constitutively endocytosed by astrocytes via the low-density lipoprotein-related protein receptor, and is then exocytosed in a regulated manner. The exocytotic recycling of tPA by astrocytes is inhibited in the presence of extracellular glutamate. Kainate receptors of astrocytes act as sensors of extracellular glutamate and, via a signaling pathway involving protein kinase C, modulate the exocytosis of tPA. Further, by thus capturing extracellular tPA, astrocytes serve to reduce NMDA-mediated responses potentiated by tPA. Overall, this work provides the first demonstration that the neuromodulator, tPA, may also be considered as a gliotransmitter.
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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.