title: Neuronal Actin Dynamics, Spine Density and Neuronal Dendritic Complexity Are Regulated by CAP2.
abstract: Actin remodeling is crucial for dendritic spine development, morphology and density. 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 Cap2(gt/gt) mice. Dendritic complexity, the number and morphology of dendritic spines were altered in Cap2(gt/gt) with increased number of excitatory synapses. This was accompanied by increased F-actin content and F-actin accumulation in cultured Cap2(gt/gt) neurons. Moreover, reduced surface GluA1 was observed in mutant neurons under basal condition and after induction of chemical LTP. Additionally, we show an interaction between CAP2 and n-cofilin, presumably mediated through the C-terminal domain of CAP2 and dependent on cofilin Ser3 phosphorylation. 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.
authors: Institute of Biochemistry I, Medical Faculty, University of Cologne, CologneGermany; Center for Molecular Medicine Cologne, University of Cologne, CologneGermany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, CologneGermany.
authors: Atul
authors: A
authors: Kumar
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, CologneGermany; Biocenter, Institute for Zoology, University of Cologne, CologneGermany.
authors: Lars
authors: L
authors: Paeger
authors: Institute of Biochemistry I, Medical Faculty, University of Cologne, CologneGermany; Center for Molecular Medicine Cologne, University of Cologne, CologneGermany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, CologneGermany.
authors: Kosmas
authors: K
authors: Kosmas
authors: Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, CologneGermany; Biocenter, Institute for Zoology, University of Cologne, CologneGermany.
authors: Peter
authors: P
authors: Kloppenburg
authors: Institute of Biochemistry I, Medical Faculty, University of Cologne, CologneGermany; Center for Molecular Medicine Cologne, University of Cologne, CologneGermany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, CologneGermany.
authors: Angelika A
authors: AA
authors: Noegel
authors: Institute of Biochemistry I, Medical Faculty, University of Cologne, CologneGermany; Center for Molecular Medicine Cologne, University of Cologne, CologneGermany; Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases, University of Cologne, CologneGermany.
authors: Vivek S
authors: VS
authors: Peche
keywords: AMPA; CAP2; actin; actin binding proteins; cyclase associated protein; dendritic spine; n-cofilin