Excitotoxicity-related endocytosis in cortical neurons |
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Authors: | Vaslin A Puyal J Borsello T Clarke P G H |
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Affiliation: | Département de Biologie Cellulaire et de Morphologie, University of Lausanne, Switzerland. anne.vaslin@unil.ch |
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Abstract: | Recent studies showed that endocytosis is enhanced in neurons exposed to an excitototoxic stimulus. We here confirm and analyze this new phenomenon using dissociated cortical neuronal cultures. NMDA-induced uptake (FITC-dextran or FITC or horseradish peroxidase) occurs in these cultures and is due to endocytosis, not to cell entry through damaged membranes; it requires an excitotoxic dose of NMDA and is dependent on extracellular calcium, but occurs early, while the neuron is still intact and viable. It involves two components, NMDA-induced and constitutive, with different characteristics. Neither component involves specific binding of the endocytosed molecules to a saturable receptor. Strikingly, molecules internalized by the NMDA-induced component are targeted to neuronal nuclei. This component, but not the constitutive one, is blocked by a c-Jun N-terminal protein kinase inhibitor. In conclusion, an excitotoxic dose of NMDA triggers c-Jun N-terminal protein kinase-dependent endocytosis in cortical neuronal cultures, providing an in vitro model of the excitotoxicity-induced endocytosis reported in intact tissues. |
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Keywords: | c-Jun N-terminal kinase dextran d-JNKI1 neurons NMDA primary culture |
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