Dendrites Are Only a CLICK Away

Abstract

STKE From one side of the neuronal cell body an axon emerges; from the other, a branched dendritic tree. These processes are crucial for the ability of a neuron to receive and transmit electrochemical signals via synapses. Neuronal activity is important in driving dendrite outgrowth, but the intermediary players are not well understood. Because neuronal activity increases intracellular Ca2+ concentration, roles for members of the family of Ca2+/calmodulin- dependent protein kinases (CaMKs) have been investigated. Takemoto-Kimura et al. have looked at CLICKIII (also known as CaMKIγ or CL3). They found that CL3 undergoes sequential lipid modifications of its C-terminal tail: prenylation, which anchors CL3 to the plasma membrane, followed by palmitoylation. Lipid fractionation experiments then showed that prenylated and palmitoylated CL3 was predominantly associated with lipid raft microdomains in the plasma membrane, and most of the lipid raft-localized CL3 was found in the proximal dendrites. Studies of rat embryonic neurons revealed that total dendrite length was enhanced by overexpression of wild-type but not kinase-deficient CL3, and knockdown of CL3 resulted in fewer and shorter dendrites. Lipid raft-localized CL3 in dendrites activated the Rho GTPase family member Rac, leading to rearrangement of the actin cytoskeleton of the growing dendrite. Together these data suggest that CL3 is a key factor in transducing Ca2+ transients into signals responsible for dendrite outgrowth. — JFF Neuron 54 , 755 (2007).