Reorganization of the actin cytoskeleton upon G-protein coupled receptor signaling

Abstract

The actin cytoskeleton is involved in a multitude of cellular responses besides providing structural support. While the role of the actin cytoskeleton in cellular processes such as trafficking and motility has been extensively studied, reorganization of the actin cytoskeleton upon signaling by G-protein coupled receptors (GPCRs) represents a relatively unexplored area. The G-protein coupled receptor superfamily is an important protein family in mammals, involved in signal transduction across membranes. G-protein coupled receptors act as major signaling hubs and drug targets. The serotonin_1A receptor is a representative member of the G-protein coupled receptor superfamily and plays a crucial role in the generation and modulation of various cognitive, developmental and behavioral functions. In order to monitor the changes in the actin cytoskeleton upon serotonin_1A receptor signaling in a quantitative manner, we developed an approach based on high magnification imaging of F-actin in cells, followed by image reconstruction. Our results suggest that the actin cytoskeleton is reorganized in response to serotonin_1A receptor signaling. In addition, we show that reorganization of the actin cytoskeleton is strongly dependent on adenosine 3',5'-cyclic monophosphate level, and is mediated by the activation of protein kinase A. Our results are consistent with the possibility of a feedback mechanism involving the actin cytoskeleton, adenosine 3',5'-cyclic monophosphate level and the serotonin_1A receptor.