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Journal Article

Neurofibromin is the major ras inactivator in dendritic spines


Yasuda,  R.
Max Planck Florida Institute for Neuroscience, Max Planck Society;

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Oliveira, A. F., & Yasuda, R. (2014). Neurofibromin is the major ras inactivator in dendritic spines. The Journal of Neuroscience: the Official Journal of the Society for Neuroscience, 34, 776-783. doi:10.1523/JNEUROSCI.3096-13.2014.

Cite as: https://hdl.handle.net/11858/00-001M-0000-0019-006F-1
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 ( approximately 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.