TY - JOUR T1 - Neuronal actin dynamics, spine density and neuronal dendritic complexity are regulated by CAP2 JF - bioRxiv DO - 10.1101/027946 SP - 027946 AU - Atul Kumar AU - Lars Paeger AU - Kosmas Kosmas AU - Peter Kloppenburg AU - Angelika A. Noegel AU - Vivek Peche Y1 - 2015/01/01 UR - http://biorxiv.org/content/early/2015/09/30/027946.abstract N2 - Actin remodeling is indispensable for dendritic spine development, morphology and density which signify learning, memory and motor skills. CAP2 is a regulator of actin dynamics through sequestering G-actin and severing F-actin. In a mouse model, ablation of CAP2 leads to cardiovascular defects and delayed wound healing. This report investigates the role of CAP2 in the brain using Cap2gt/gt mice. Dendritic spine density and neuronal dendritic length were altered in Cap2gt/gt. This was accompanied by increased F-actin content and F-actin accumulation in cultured Cap2gt/gt neurons. In membrane depolarization assays, Cap2gt/gt synaptosomes exhibit an impaired F/G actin ratio, indicating altered actin dynamics. We show an interaction between CAP2 and n-cofilin, presumably mediated through the C-terminal domain of CAP2 and is cofilin ser3 phosphorylation dependent. In vivo, the consequences of this interaction were altered phosphorylated cofilin levels and formation of cofilin aggregates in the neurons. Thus, our studies identify a novel role of CAP2 in neuronal development and neuronal actin dynamics. ER -