title: Excitotoxicity-related endocytosis in cortical neurons.
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.
authors: Département de Biologie Cellulaire et de Morphologie, University of Lausanne, Switzerland. anne.vaslin@unil.ch
authors: A
authors: A
authors: Vaslin
authors: J
authors: J
authors: Puyal
authors: T
authors: T
authors: Borsello
authors: P G H
authors: PG
authors: Clarke
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D003911:Dextrans; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D008954:Models, Biological; D016202:N-Methylaspartate / Q000633:toxicity; D009410:Nerve Degeneration / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D003911:Dextrans; D018690:Excitatory Amino Acid Agonists; D009498:Neurotoxins; C015219:fluorescein isothiocyanate dextran; D016202:N-Methylaspartate; D048031:JNK Mitogen-Activated Protein Kinases; D016650:Fluorescein-5-isothiocyanate