Tissue-type plasminogen activator induces synaptic vesicle endocytosis in cerebral cortical neurons

Neuroscience
M YepesL Cheng

Abstract

The release of the serine proteinase tissue-type plasminogen activator (tPA) from the presynaptic terminal of cerebral cortical neurons plays a central role in the development of synaptic plasticity, adaptation to metabolic stress and neuronal survival. Our earlier studies indicate that by inducing the recruitment of the cytoskeletal protein βII-spectrin and voltage-gated calcium channels to the active zone, tPA promotes Ca(2+)-dependent translocation of synaptic vesicles (SVs) to the synaptic release site where they release their load of neurotransmitters into the synaptic cleft. Here we used a combination of in vivo and in vitro experiments to investigate whether this effect leads to depletion of SVs in the presynaptic terminal. Our data indicate that tPA promotes SV endocytosis via a mechanism that does not require the conversion of plasminogen into plasmin. Instead, we show that tPA induces calcineurin-mediated dynamin I dephosphorylation, which is followed by dynamin I-induced recruitment of the actin-binding protein profilin II to the presynaptic membrane, and profilin II-induced F-actin formation. We report that this tPA-induced sequence of events leads to the association of newly formed SVs with F-actin clusters in the ...Continue Reading

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Citations

May 2, 2017·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Niko Hensel, Peter Claus
Feb 9, 2017·Schizophrenia Bulletin·Erin J FeeneyPhilip R Corlett
Mar 17, 2018·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Valerie JeanneretManuel Yepes
May 5, 2017·Neural Regeneration Research·Valerie Jeanneret, Manuel Yepes
Apr 2, 2019·Frontiers in Cell and Developmental Biology·Ewa E Bres, Andreas Faissner
May 21, 2019·Frontiers in Cellular Neuroscience·Sophie LenoirDenis Vivien

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