Application of percolation theory principles to the analysis of interaction of adenylate cyclase complex proteins in cell membranes.

Abstract

Lateral protein movement in cell membranes takes place in a medium with 'obstacles'. These obstacles are: (a) aggregates of major integral proteins immobilized by submembranous structures and cytoskeleton, and (b) membrane lipids in the gel phase. Hormonal activation of the adenylate cyclase complex is associated with lateral mobility of the constiutent proteins. Modification of the interaction of these proteins due to variation of the 'fluid' lipid fraction in reticulocyte membranes has been studied. A decrease in the percentage of 'fluid' lipids in membranes resulted in the inhibition (up to the full cessation) of the interaction of beta-adrenoreceptors with regulatory NS-proteins. The interaction of NS-proteins with catalytic proteins stopped as well. On the other hand, an increase in the 'fluid' lipid fraction led to a more intensive interaction. These facts do not arise from the functional damage of interacting proteins. Consequently, hormonal activation of the adenylate cyclase complex depends on the fraction of 'fluid' lipids in the membrane. The data obtained are in conformity with the percolation theory which makes it possible to characterize long-distance protein movement in a medium ('fluid' lipids) containing obstacles. Thus, interacting proteins prove to diffuse within distances greatly exceeding protein sizes. As a consequence, the intrinsic activity of a beta-agonist, isoproterenol, varies from 1 to 0 depending on the 'fluid' lipid fraction. Our findings also suggest that in vitro there are no beta-receptors precoupled with NS-proteins in rat reticulocyte membranes in the absence of guanine nucleotides.