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NMDA ReceptorActivation MediatesCopper Homeostasis inHippocampal Neurons Michelle L. SchliefAnn Marie CraigJonathan D. Gitlin2005 год

NMDA Receptor Activation Mediates Copper Homeostasis in Hippocampal Neurons
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Аннотация: Copper is an essential transition metal with a critical role in the CNS. This requirement is underscored by Menkes disease, a fatal neurodegenerative disorder of childhood resulting from the absence or dysfunction of a copper-transporting P-type ATPase. To elucidate the cell biological mechanisms of copper homeostasis in the CNS, a polyclonal antisera against Menkes ATPase was used in immunoblot and immunohistochemical studies, demonstrating abundant expression of this copper transporter in hippocampal neurons. Consistent with this observation, immunofluorescent analysis revealed Menkes ATPase in the late Golgi of hippocampal neurons in primary culture. Glutamate receptor activation was found to result in the rapid and reversible trafficking of Menkes ATPase to neuronal processes, independent of the intracellular copper concentration and specific for activation of the NMDA- but not AMPA/kainate-type glutamate receptors. Metabolic studies revealed that trafficking of Menkes ATPase after NMDA receptor activation is associated with rapid release of copper from hippocampal neurons. Menkes ATPase is directly required for this copper efflux, because similar studies in hippocampal neurons derived from mice lacking a functional Menkes ATPase demonstrated no copper release. Together, these data reveal a critical role for Menkes ATPase in the availability of an NMDA receptor-dependent, releasable pool of copper in hippocampal neurons and demonstrate a unique mechanism linking copper homeostasis and neuronal activation within the CNS.
Год издания: 2005
Авторы: Michelle L. Schlief, Ann Marie Craig, Jonathan D. Gitlin
Издательство: Society for Neuroscience
Источник: Journal of Neuroscience
Ключевые слова: Trace Elements in Health, Neuroscience and Neuropharmacology Research, Heavy Metal Exposure and Toxicity
Другие ссылки: Journal of Neuroscience (PDF)
Journal of Neuroscience (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)