ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2015
Tissue-type plasminogen activator triggers the synaptic vesicle cycle in cerebral cortical neurons.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 31 citations in OpenAlex.
- The involvement of the synaptic vesicle cycle in homocysteine induced neurotoxicity in vitro and in vivo.Scientific reports · 2025Article
- Tissue-type plasminogen activator induces conditioned receptive field plasticity in the mouse auditory cortex.iScience · 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
- Tissue Plasminogen Activator in Central Nervous System Physiology and Pathology: From Synaptic Plasticity to Alzheimer's Disease.Seminars in thrombosis and hemostasis · 2022Review
- Urokinase-type plasminogen activator is a modulator of synaptic plasticity in the central nervous system: implications for neurorepair in the ischemic brain.Neural regeneration research · 2020Review
- Urokinase-type plasminogen activator (uPA) regulates the expression and function of growth-associated protein 43 (GAP-43) in the synapse.The Journal of biological chemistry · 2020Article
- The role of endogenous tissue-type plasminogen activator in neuronal survival after ischemic stroke: friend or foe?Cellular and molecular life sciences : CMLS · 2019Review
- Tissue-type plasminogen activator regulates p35-mediated Cdk5 activation in the postsynaptic terminal.Journal of cell science · 2019Article
- Low Density Receptor-Related Protein 1 Interactions With the Extracellular Matrix: More Than Meets the Eye.Frontiers in cell and developmental biology · 2019Review
- Post-synaptic Release of the Neuronal Tissue-Type Plasminogen Activator (tPA).Frontiers in cellular neuroscience · 2019Article
- Tissue-type plasminogen activator protects the postsynaptic density in the ischemic brain.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2018Article
- In vitro and Ex vivo Neurotoxic Effects of Efavirenz are Greater than Those of Other Common Antiretrovirals.Neurochemical research · 2017Article
- Tissue-type plasminogen activator is a homeostatic regulator of synaptic function in the central nervous system.Neural regeneration research · 2017Review
- Clarithromycin increases neuronal excitability in CA3 pyramidal neurons through a reduction in GABAergic signaling.Journal of neurophysiology · 2017Article
- Recent progress in translational research on neurovascular and neurodegenerative disorders.Restorative neurology and neuroscience · 2017Review
- Tissue-type plasminogen activator induces synaptic vesicle endocytosis in cerebral cortical neurons.Neuroscience · 2016Article
- The Plasminogen Activation System Promotes Dendritic Spine Recovery and Improvement in Neurological Function After an Ischemic Stroke.Translational stroke research · 2016Article
- Tissue-type plasminogen activator is a modulator of the synaptic vesicle cycle.Neural regeneration research · 2016Article
- Tissue-type Plasminogen Activator (tPA) Modulates the Postsynaptic Response of Cerebral Cortical Neurons to the Presynaptic Release of Glutamate.Frontiers in molecular neuroscience · 2016Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The active zone (AZ) is a thickening of the presynaptic membrane where exocytosis takes place. Chemical synapses contain neurotransmitter-loaded synaptic vesicles (SVs) that at rest are tethered away from the synaptic release site, but after the presynaptic inflow of Ca(+2) elicited by an action potential translocate to the AZ to release their neurotransmitter load. We report that tissue-type plasminogen activator (tPA) is stored outside the AZ of cerebral cortical neurons, either intermixed with small clear-core vesicles or in direct contact with the presynaptic membrane. We found that cerebral ischemia-induced release of neuronal tPA, or treatment with recombinant tPA, recruits the cytoskeletal protein βII-spectrin to the AZ and promotes the binding of SVs to βII-spectrin, enlarging the population of SVs in proximity to the synaptic release site. This effect does not require the generation of plasmin and is followed by the recruitment of voltage gated calcium channels (VGCC) to the presynaptic terminal that leads to Ca(+2)-dependent synapsin I phosphorylation, freeing SVs to translocate to the AZ to deliver their neurotransmitter load. Our studies indicate that tPA activates the SV cycle and induces the structural and functional changes in the synapse that are required for successful neurotransmission.
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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.