Neuronal Rho GEFs in Synaptic Physiology and Behavior

In the mammalian brain, the majority of excitatory synapses are housed in micron-sized dendritic protrusions called spines, which can undergo rapid changes in shape and number in response to increased or decreased synaptic activity. These dynamic alterations in dendritic spines require precise control of the actin cytoskeleton. Within spines, multidomain Rho guanine nucleotide exchange factors (Rho GEFs) coordinate activation of their target Rho GTPases by a variety of pathways. In this review, we focus on the handful of disease-related Rho GEFs (Kalirin; Trio; Tiam1; P-Rex1,2; RasGRF1,2; Collybistin) localized at synapses and known to affect electrophysiology, spine morphology, and animal behavior. The goal is to integrate structure/function studies with measurements of synaptic function and behavioral phenotypes in animal models.