The mechanisms underlying the spatial spreading of signaling activity

During the induction of plasticity of dendritic spines, many intracellular signaling pathways are spatially and temporally regulated to co-ordinate downstream cellular processes in different dendritic micron-domains. Recent advent of imaging technology based on fluorescence resonance energy transfer (FRET) has allowed the direct monitoring of the spatiotemporal regulation of signaling activity in spines and dendrites during synaptic plasticity. In particular, the activity of three small GTPase proteins HRas, Cdc42, and RhoA, which share similar structure and mobility on the plasma membrane, displayed different spatial spreading patterns: Cdc42 is compartmentalized in the stimulated spines while RhoA and HRas spread into dendrites over 5-10 μm. These measurements thus provide the basis for understanding the mechanisms underlying the spatiotemporal regulation of signaling activity. Further, using spatiotemporally controlled spine stimulations, some of the roles of signal spreading have been revealed.

► FRET imaging provides means to study the spatiotemporal dynamics of intracellular signaling in synaptic compartments. ► The activity of three small GTPase proteins HRas, Cdc42 and RhoA displayed different spatial spreading patterns. ► The spatial spreading of small GTPase signaling can be mathematically modeled. ► Some of the roles of signal spreading have been revealed.