Membrane-bound receptor

A typical force curve showing the specific avidin-biotin interaction is depicted in figure Bl.20.10. The SFA revealed the strong influence of hydration forces and membrane undulation forces on the specific binding of proteins to membrane-bound receptors [81]. 

Fig. 1.—Diagrammatic Representation of the Three Steps in the Taste-cell Transduction. Step 1, interaction of stimulus (S) with membrane-bound receptor (R) to form stimulus-receptor complex (SR) step 2, conformational change (SR) to (SR), brought about by interaction of S with R (this change initiates a change in plasma-membrane conformation of taste cells, probably below the level of the tight junction) and step 3, conformational changes of the membrane result in lowered membrane resistance, and the consequential influx on intracellular ionic species, probably Na. This influx generates the receptor potential which induces synaptic vesicular release to the innervating, sensory nerve, leading to the generator potential.

Inositol triphosphate (IP3)-gated channels are also associated with membrane-bound receptors for hormones and neurotransmitters. In this case, binding of a given substance to its receptor causes activation of another membrane-bound protein, phospholipase C. This enzyme promotes hydrolysis of phosphatidylinositol 4,5-diphosphate (PIP2) to IP3. The IP3 then diffuses to the sarcoplasmic reticulum and opens its calcium channels to release Ca++ ions from this intracellular storage site. 

Screening the molecular heterogeneity of receptor expression in endothelial cell surfaces is required for the development of vascular-targeted therapies. First, as opposed to targeting purified proteins as discussed above, membrane-bound receptors are more likely to preserve their functional conformation, which can be lost upon purification and immobilization outside the context of intact cells. Moreover, many cell surface receptors require the cell membrane microenvironment to function so that protein-protein interaction may occur. Finally, combinatorial approaches may allow the selection of cell membrane ligands in a functional assay and without any bias about the cellular surface receptor. Therefore, even as yet unidentified receptors may be targeted. 

Besanger, T.R., Easwaramoorthy, B. and Brennan, J.D. (2004) Entrapment of highly active membrane-bound receptors in macroporous sol-gel derived silica. Analytical Chemistry, 76, 6470-6475. 

Quast U, Schimerlik M I, Raftery MA. 1979. Ligand-induced changes in membrane-bound receptor observed by ethi-dium fluorescence. Biochemistry 18 1891-1901. 

The process of RGS recruitment to the membrane-bound receptor, however, seems to be constitutive—it appears to be independent of the state of activation of the receptor or G protein. This recruitment may facilitate signal quenching because the combination of 30 RGS proteins and 20 Ga subunits allows for a diverse pattern of inactivation. RGS proteins, therefore, are recruited to the plasma membrane in cells expressing either Ga subunits (Gsa) or linked GPCRs (e.g., Dj-dopamine receptor) in preparation for the GAP activity that quenches G protein signaling (104,105). 

There are no inherent limitations to the nature of the interaction that can be probed with the FAC method. This too stems from an uncoupling of the binding event and the detector. The method can be applied to simple binary interactions between protein and small molecule, but also to protein-protein interactions, protein-cell interactions and virtually any interaction that can be modeled in a flow system. Some of the more elegant examples include drug interaction with whole cells [12] and membrane-bound receptors from brain homogenates [13]. Ultimately, the limitations are dictated by what can be detected from a stream of column effluent. 

D., Melch, M., McConkey, M., Bergeron, J., Wong, S. K.-E. fully automated radioligand binding filtration assay for membrane-bound receptors. BioTechniques 2002, 33, 932-937. 

Membrane-bound receptors bind the intrinsic neurotransmitter (autoreceptor) or transmitters of neighboring neurons (heteroreceptor) and affect the cell via intracellular messengers. One response, for example, is the modulation of neurotransmitter release (Tanger, 1997). 

The receptors through which neurotrophins act belong to a third class of membrane-bound receptors, which possess intracellular kinase activity. These receptors, called receptor tyrosine kinases, are composed of... 

In some cases, a ligand that acts as an agonist at membrane-bound receptors increases the activity of an intracellular second messenger Activation of membrane-bound receptors and subsequent intracellular events elicit a biologic response through the transcription of DNA... 

Cell surface receptors receive the signal (e.g. a chemical messenger) at the outside of the cell, become activated and initiate a signaling chain in the interior of the cell. In such signaling pathways the membrane bound receptor transduces the signal at the cell membrane so that it is not necessary for the signal to actually enter the cell. 

The receptors of the target cell can be divided into two classes the membrane bound receptors and the soluble cytoplasmic or nuclear localized receptors (fig. 3.6). 

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