Abstract
The possible structural organization of surface membrane receptors, heterotrimeric GTP-binding regulatory proteins (G-proteins), and effectors (adenylyl cyclase, phospholipases, phosphodiesterases, ion channels, etc.) is a major unresolved question. The physical relationship between these elements has been discussed in an insightful review of the role of G-proteins in signal transduction (NeeR and Clapham 1988). One of the questions raised is whether the components of signal transduction are free to move (“float”) in the plane of the membrane and interact in accordance with their relative affinities for each other. Given nature’s propensity to spatially organize and regulate structures in a highly specialized, nonrandom fashion, perhaps the question should be posed: how are receptors, transducers, and effectors spatially organized for rapid, efficient, and reversible interactions that only allow restricted diffusion of the components? There is evidence that receptors are precoupled to G-proteins in the absence of agonists (for example, see Watanabe et al. 1986). As discussed elsewhere in detail (Rodbell 1991; Rodbell 1992), there are many reasons to believe that receptors are coupled with heterotrimeric G-proteins structured in the form of multimers. As in the case of membrane proteins attached to filamental actin, it is likely that such large structures have restricted mobility in the membrane. As for effectors, it has been suggested that adenylyl cyclase is linked, indirectly or directly, to actin (Watson 1990). Other potential effectors such as sodium and calcium channels also appear to be associated with actin through the actin-binding protein ankyrin (Davis and Bennett 1990; Edelstein et al. 1988), implying organized, fixed locations of effectors associated with the intracellular cytoskeletal matrix. If such organization applies to all signal transduction systems, it must be concluded that some type of signal is emitted from the receptor—G-protein complex that can be rapidly and reversibly conveyed between immobilized receptor—G-protein complexes and immobilized effectors.
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Rodbell, M., Jahangeer, S., Coulter, S. (1993). G-Proteins Have Properties of Multimeric Proteins: An Explanation for the Role of GTPases in their Dynamic Behavior. In: Dickey, B.F., Birnbaumer, L. (eds) GTPases in Biology II. Handbook of Experimental Pharmacology, vol 108 / 2. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-78345-6_1
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