RT Journal Article
SR Electronic
T1 Neuronal actin dynamics, spine density and neuronal dendritic complexity are regulated by CAP2
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 027946
DO 10.1101/027946
A1 Atul Kumar
A1 Lars Paeger
A1 Kosmas Kosmas
A1 Peter Kloppenburg
A1 Angelika A. Noegel
A1 Vivek Peche
YR 2015
UL http://biorxiv.org/content/early/2015/09/30/027946.abstract
AB 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.