Title: Mobility of G Proteins is Heterogeneous and Polarized During Chemotaxis
Abstract: The interaction of G-protein-coupled receptors with G proteins is a key event in transmembrane signal transduction leading to vital decision-taking of the cell. Here we applied single-molecule epifluorescence microscopy to study the mobility of both the Gβγ and the Gα2 subunits of the G protein heterotrimer in comparison to the cAMP-receptor responsible for chemotactic signaling in Dictyostelium discoideum. Our experimental results suggest that ∼30% of the G protein heterotrimers exist in receptor pre-coupled complexes. Upon stimulation in a chemotactic gradient this complex dissociates, subsequently leading to a linear diffusion/collision amplification of the external signal. The further observation of partial immobilization and confinement of Gβγ in an agonist, F-actin and Gα2-dependent fashion led to the hypothesis of functional nanometric domains in the plasma membrane that locally restrict the activation signal and in turn lead to faithful and efficient chemotactic signaling.