Fig. P1.

NMDAR activation leads to β-arrestin-2–dependent cofilin translocation into dendritic spines, inducing remodeling. NMDAR activation and Ca²⁺ influx into the neuron promote an intracellular signaling cascade that leads to (i) cofilin activation through dephosphorylation (the removal of phosphate groups). (ii) β-Arrestin-2 binds and translocates active cofilin to dendritic spines (the parts of neurons that receive information from other neurons). (iii) The actin-severing activity of cofilin leads to remodeling of mature, mushroom-shaped spines into immature thin spines and filopodia (slender cell projections). Abbreviations: β-arr2, β-arrestin-2; Cof, cofilin; NMDAR, N-methyl-d-aspartate receptor.