Spines and neurite branches function as geometric attractors that enhance protein kinase C action

Ca²⁺ and diacylglycerol-regulated protein kinase Cs (PKCs; conventional PKC isoforms, such as PKC[gamma]) are multifunctional signaling molecules that undergo reversible plasma membrane translocation as part of their mechanism of activation. In this article, we investigate PKC[gamma] translocation in hippocampal neurons and show that electrical or glutamate stimulation leads to a striking enrichment of PKC[gamma] in synaptic spines and dendritic branches. Translocation into spines and branches was delayed when compared with the soma plasma membrane, and PKC[gamma] remained in these structures for a prolonged period after the response in the soma ceased. We have developed a quantitative model for the translocation process by measuring the rate at which PKC[gamma] crossed the neck of spines, as well as cytosolic and membrane diffusion coefficients of PKC[gamma]. Our study suggests that neurons make use of a high surface-to-volume ratio of spines and branches to create a geometric attraction process for PKC that imposes a delayed enhancement of PKC action at synapses and in peripheral processes.