G-proteins, transducin

Rhodopsin is a 7-pass receptor coupled to the trimeric G protein transducin (G ). 

Klinker IF, Seifert R (1997) Morphine and muscle relaxants are receptor-independent G-protein activators and cromolyn is an inhibitor of stimulated G-protein activity. Inflamm Res 46 46—50 Klinker IF, Seifert R, Datum H, Rommelspacher H (1997) Activation by beta-carbohnes of G-proteins in HL-60 membranes and the bovine retinal G-protein transducin in a receptor-independent manner. Biochem Pharmacol 53 1621-1626... 

In the visual process a light signal is received by the photoreceptors, rhodopsin, of the rod cells which are then converted to the activated state, R. The activated rhodopsin passes the signal on to the cognate G-protein, transducin, which in turn activates the next effector molecule, a cGMP phosphodiesterase. The phophodiesterase hydro-... 

The best investigated is the desensitization of the adrenaline receptor type P2 and of rhodopsin. Rhodopsin has the function of a light receptor in the process of vision, ft receives light signals and conducts them to the relevant G-protein, transducin. The key reaction in desensitization of both systems is the phosphorylation of the receptor at the cytoplasmic side by specific protein kinases. 

Fig. 5.15. ADP-ribosylation of the Ga-subunit of transdudn by cholera toxin. Cholera toxin catalyzes the ADP-ribosylation of the a-subunit of the G-protein transducin. During the reaction, the ADP-ribose residue of NAD+ is transferred to Argl74 of Ga which inactivates the GTPase activity of Ga i-...

Excited Rhodopsin Acts through the G Protein Transducin to Reduce the cGMP Concentration... 

In rod and cone cells of the retina, light activates rhodopsin, which stimulates replacement of GDP by GTP on the G protein transducin. The freed a subunit of transducin activates cGMP phosphodiesterase, which lowers [cGMP] and thus closes cGMP-dependent ion channels in the outer segment of the neuron. The resulting hyperpolarization of the rod or cone cell carries the signal to the next neuron in the pathway, and eventually to the brain. 

Activation of the phosphodiesterase by light requires the presence of GTP and is associated with the binding of GTP to another protein, transducin. Transducin is a member of the family of G proteins that participate in the activation or inhibition of adenylate cyclase by hormones in other tissues (see chapter 24). Like other G proteins, transducin consists of three subunits, a, (3, and y (fig. S2.12). In the resting state, the a subunit contains a molecule of bound GDP. When rhodopsin is transformed to metarhodopsin II by light, it interacts with transducin, causing GTP to displace the bound GDP. Once GTP is attached, the a subunit probably separates from the (3 and y subunits and binds to an inhibitory subunit of the phosphodiesterase. The removal of the inhibitory component activates the phosphodiesterase. 

Natochin, M., Granovsky, A. E., and Artemyev, N. O. (1998a). Identification of effector residues on photoreceptor G protein, transducin./. Biol. Chem. 273, 21808-21815. 

In the dark, the sodium channels are kept open, and there is a dark current because they bind GMP. They are closed by the loss of this bound GMP as it is hydrolyzed to 5 -GMP by phosphodiesterase. The phosphodiesterase is activated by the guanine nucleotide binding protein (G-protein) transducin. 

Like other G-proteins, transducin has innate GTPase activity, and over a time course of seconds or less is autocatalytically converted to transducin-GDP, which does not interact with phosphodiesterase. This restores the normal inhibition of phosphodiesterase, permitting cGMP concentrations to rise again, reopening the sodium channels and restoring the dark current. 

Two-thirds of the energy acquired from the absorption of the photon remains in the opsin protein. From this energy-rich state rhodopsin passes through several intermediate states on the way to the signalling state which is able to bind and activate the G protein, transducin. The 9-methyl group of retinal is the allosteric trigger that opens the cross-talk... 

Ffe. 5.11 TLie MM forms of rhodopsin (R) are in equilibrium with their parent compound Ml and the progeny Mill. The equilibnum between the metastates, Ml, Mila, and Mllb, are attained within a few milliseconds after illumination. The Ml/Mlla transition is accompanied by the intramolecular translocation of the Schiff-base proton to GlullS, located in a region close to the lipid membrane. The subsequent Mlla/Mllb transition is dependent on proton uptake from the aqueous phase and occurs in a watersxposed area. Fast binding of the G protein, transducin, occurs only with Mllb.(Reproduced from ref. 58 with permission of Elsevier Science.)... 

Binding of the nucleotide, GTP, to the G protein, transducin, and binding of the G protein to activated rhodopsin, R, are mutually exclusive. It follows that the nucleotide-binding site on the a-subunit of the G protein must be empty when the... 

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