RasGRF2 Rac-GEF activity couples NMDA receptor calcium flux to enhanced synaptic transmission.
Dendritic spines are the primary sites of excitatory synaptic transmission in the vertebrate brain, and the morphology of these actin-rich structures correlates with synaptic function. Here we demonstrate a unique method for inducing spine enlargement and synaptic potentiation in dispersed hippocampal neurons, and use this technique to identify a coordinator of these processes; Ras-specific guanine nucleotide releasing factor 2 (RasGRF2). RasGRF2 is a dual Ras/Rac guanine nucleotide exchange factor (GEF) that is known to be necessary for long-term potentiation in situ. Contrary to the prevailing assumption, we find RasGRF2's Rac-GEF activity to be essential for synaptic potentiation by using a molecular replacement strategy designed to dissociate Rac- from Ras-GEF activities. Furthermore, we demonstrate that Rac1 activity itself is sufficient to rapidly modulate postsynaptic strength by using a photoactivatable derivative of this small GTPase. Because Rac1 is a major actin regulator, our results support a model where the initial phase of long-term potentiation is driven by the cytoskeleton.
Department of Neuroscience, Baylor College of Medicine, Houston, TX 77030, USA.
Brandon
B
Schwechter
Christian
C
Rosenmund
Kimberley F
KF
Tolias
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002478:Cells, Cultured; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D009435:Synaptic Transmission; D020663:ras Guanine Nucleotide Exchange Factors / Q000378:metabolism*
D020662:Guanine Nucleotide Exchange Factors; C504490:RASGRF2 protein, human; D016194:Receptors, N-Methyl-D-Aspartate; D020663:ras Guanine Nucleotide Exchange Factors; D002118:Calcium
AMPA receptor; LTP; Rho GTPase; synaptic plasticity