Clustering of membrane proteins in the pre-stimulation stage is required for signal transduction: a computer analysis

Abstract

The physiological significance of membrane protein clustering for signal transduction was examined theoretically using a Monte Carlo computer simulation. Simulation results revealed that pre-stimulation clustering of membrane proteins enhanced signal transduction. Membrane protein clustering induced by the binding of external stimuli provided no kinetic advantage in terms of formation rate or maximum quantity of active membrane receptor complexes. These data suggested that membrane proteins associate weakly in the clustering areas of non-stimulated cells, and that their association is strengthened upon binding of extracellular stimuli to the membrane receptor. Additionally, the number of cytosolic proteins recruited to membrane receptor complexes was not increased by the membrane complex clustering, except when cytosolic signal proteins were localized to a narrow area such as a tunnel that ran from the membrane cluster to the nucleus. Simulations were carried out on a conventional personal computer under Windows XP or 2000 operating systems. Since neither special computing hardware nor special training is required, our simulation procedure could be easily adapted for kinetic analysis of any signal transduction pathway.