The diacylglycerol-binding protein α1-chimaerin regulates dendritic morphology

The morphological and functional differentiation of neuronal dendrites is controlled through transcriptional programs and cell–cell signaling. Synaptic activity is thought to play an important role in the maturation of dendritic arbors, but the signaling pathways that couple neuronal activity and morphological changes in dendrites are not well understood. We explored the function of α1-chimaerin, a neuronal diacylglycerol-binding protein with a Rho GTPase-activating protein domain that inactivates Rac1. We find that stimulation of phospholipase Cβ-coupled cell surface receptors recruits α1-chimaerin to the plasma membrane of cultured hippocampal neurons. We further show that α1-chimaerin protein levels are controlled by synaptic activity and that increased α1-chimaerin expression results in the pruning of dendritic spines and branches. This pruning activity requires both the diacylglycerol-binding and Rac GTPase-activating protein activity of α1-chimaerin. Suppression of α1-chimaerin expression resulted in increased process growth from the dendritic shaft and from spine heads. Our data suggest that α1-chimaerin is an activity-regulated Rho GTPase regulator that is activated by phospholipase Cβ-coupled cell surface receptors and contributes to pruning of dendritic arbors