title: Neurofibromin is the major ras inactivator in dendritic spines.
abstract: In dendritic spines, Ras plays a critical role in synaptic plasticity but its regulation mechanism is not fully understood. Here, using a fluorescence resonance energy transfer/fluorescence lifetime imaging microscopy-based Ras imaging technique in combination with 2-photon glutamate uncaging, we show that neurofibromin, in which loss-of-function mutations cause Neurofibromatosis Type 1 (NF1), contributes to the majority (∼90%) of Ras inactivation in dendritic spines of pyramidal neurons in the CA1 region of the rat hippocampus. Loss of neurofibromin causes sustained Ras activation in spines, which leads to impairment of spine structural plasticity and loss of spines in an activity-dependent manner. Therefore, deregulation of postsynaptic Ras signaling may explain, at least in part, learning disabilities associated with NF1.
authors.affiliation: Department of Neurobiology, Duke University Medical Center, Durham, North Carolina 27710, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, Max-Planck Florida Institute for Neuroscience, Jupiter, Florida 33458, and Doctoral Program in Biomedicine and Experimental Biology, Center for Neuroscience and Cell Biology, University of Coimbra, 3004-517 Coimbra, Portugal.
authors.forename: Ana F
authors.initials: AF
authors.lastname: Oliveira
authors.forename: Ryohei
authors.initials: R
authors.lastname: Yasuda
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000235:genetics / Q000502:physiology* / Q000648:ultrastructure; D019706:Excitatory Postsynaptic Potentials / Q000235:genetics; D005260:Female; D011905:Genes, ras / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology / Q000648:ultrastructure; D017774:Long-Term Potentiation / Q000502:physiology; D008297:Male; D025542:Neurofibromin 1 / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D009924:Organ Culture Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D025542:Neurofibromin 1
keywords: LTP; NF1; NMDA receptor; hippocampus; rats; small GTPase; synaptic plasticity