title: Explicit spatiotemporal simulation of receptor-G protein coupling in rod cell disk membranes.
abstract: Dim-light vision is mediated by retinal rod cells. Rhodopsin (R), a G-protein-coupled receptor, switches to its active form (R(∗)) in response to absorbing a single photon and activates multiple copies of the G-protein transducin (G) that trigger further downstream reactions of the phototransduction cascade. The classical assumption is that R and G are uniformly distributed and freely diffusing on disk membranes. Recent experimental findings have challenged this view by showing specific R architectures, including RG precomplexes, nonuniform R density, specific R arrangements, and immobile fractions of R. Here, we derive a physical model that describes the first steps of the photoactivation cascade in spatiotemporal detail and single-molecule resolution. The model was implemented in the ReaDDy software for particle-based reaction-diffusion simulations. Detailed kinetic in vitro experiments are used to parametrize the reaction rates and diffusion constants of R and G. Particle diffusion and G activation are then studied under different conditions of R-R interaction. It is found that the classical free-diffusion model is consistent with the available kinetic data. The existence of precomplexes between inactive R and G is only consistent with the data if these precomplexes are weak, with much larger dissociation rates than suggested elsewhere. Microarchitectures of R, such as dimer racks, would effectively immobilize R but have little impact on the diffusivity of G and on the overall amplification of the cascade at the level of the G protein.
authors.affiliation: Department of Mathematics, Computer Science and Bioinformatics, Freie Universität Berlin, Berlin, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Schöneberg
authors.affiliation: Institut für Medizinische Physik und Biophysik, Charité, Universitätsmedizin Berlin, Berlin, Germany. Electronic address: martin.heck@charite.de.
authors.forename: Martin
authors.initials: M
authors.lastname: Heck
authors.affiliation: Institut für Medizinische Physik und Biophysik, Charité, Universitätsmedizin Berlin, Berlin, Germany.
authors.forename: Klaus Peter
authors.initials: KP
authors.lastname: Hofmann
authors.affiliation: Department of Mathematics, Computer Science and Bioinformatics, Freie Universität Berlin, Berlin, Germany. Electronic address: frank.noe@fu-berlin.de.
authors.forename: Frank
authors.initials: F
authors.lastname: Noé
mesh_terms: D003198:Computer Simulation; D004058:Diffusion; D007700:Kinetics; D008958:Models, Molecular; D055668:Photochemical Processes; D017948:Retinal Rod Photoreceptor Cells / Q000737:chemistry*; D012243:Rhodopsin / Q000737:chemistry*; D012984:Software; D015293:Transducin / Q000737:chemistry*; D014741:Video Recording
chemical_list: D012243:Rhodopsin; D015293:Transducin