Protein receptor hypotheses

Hemmings, W.A., and E.W. Williams, The attachment of IgG to cell components a reconsideration of BrambelTs receptor hypothesis of protein transmission. Proc R Soc Lond B Biol Sci, 1974. 187(1087) 209-19. 

Protein transport between intracellular compartments is mediated by a mechanism that is well-conserved among all eukaryotes, from yeast to man. The transport mechanism involves carrier vesicles that bud from one organelle and fuse selectively to another. Specialized proteins are required for vesicle transport, docking, and fusion, and they have been generically named SNAREs (an acronym for soluble N-ethylma-leimide-sensitive fusion attachment protein receptor). SNAREs have been divided into those associated with the vesicle (termed v-SNAREs), and those associated with the target (termed t-SNAREs). The key protein, which led to the discovery of SNAREs was NSF, an ATPase found ubiquitously in all cells, and involved in numerous intracellular transport events. The subsequent identification of soluble proteins stably bound to NSF, the so-called SNARE complex, led to the formulation of the SNARE hypothesis, which posits that all intracellular fusion events are mediated by SNAREs (Rothman, 2002). 

The first demonstration of intracellular receptors was the finding of target tissues in the uterus (Jensen and Jacobson, 1960). A generalized steroid-receptor hypothesis has evolved since then in which the putative intracellular cytoplasmic protein is activated. The specific steroid enters the cell as a free compound, but arrives at its target in a mostly protein-bound form. Following activation the complete steroid-receptor complex is translocated to the... 

Figure 5.1. Shallenberger and Acree hypothesis for the interaction of the AH and B units of a sweet compound, with complementary groups on the sweet-tasting protein receptor.

L-type Ca channels are primarily regulated by voltage and are thus opened and closed in response to changes in membrane potential, but in addition, they are regulated by receptor-dependent processes involving protein phosphorylation and G-proteins (Fig. 2). Many lines of evidence support the hypothesis that Ca channels are regulated by phosphorylation by several protein kinases, in particular by... 

If ft receptors couple to K+ channels and adenylyl cyclase via different G proteins, it is possible that chronic morphine treatment uncouples the receptor from those G proteins linked to the K+ channel and not those coupling fi receptors to adenylyl cyclase. Such a hypothesis would require that G proteins couple to different intracellular domains of the fi receptor so that interaction of G proteins with some domains could be blocked by post-translational events, such as phosphorylation, whereas binding of G proteins to other fi receptor domains would not be affected. 

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