Interaction between distinct actin pools controls activity-dependent actin dynamics in the dendritic spine

Actin cytoskeleton is composed of functionally distinct pools of filamentous (F)-actin defined by their regulatory machinery and dynamics. Although these networks may compete for actin monomers and regulatory factors, the interaction between them remains poorly understood. Here, we show that disruption of the labile F-actin pool in neurons by limited actin depolymerization unexpectedly triggers rapid enhancement of the F-actin content at the dendritic spine. Long-term blockade of NMDA-type receptors decreases spine actin polymerization, which is specifically restored by the labile pool ablation. Increase in the spine actin is triggered by blockade of formin-induced actin polymerization in a manner dependent on Arp2/3 complex activity. Finally, limited actin depolymerization increases F-actin levels in a cultured cell line, suggesting the generality of the two-tiered actin dynamics. Based on these findings, we propose a model whereby the labile pool of Factin controlled by formin restricts the polymerization state of the Arp2/3regulated stable spine actin, suggesting a feedback principle at the core of cytoskeletal organization in neurons.