Adenylyl cyclase signal transduction

Berghard A. and Buck L.B. (1996). Sensory transduction in vomeronasal neurons evidence for G-alpha-o, G-alpha-i2, and adenylyl cyclase II as major components of a pheromone signaling cascade. J Neurosci 16, 909-918. 

FIGURE 14-6 Main signaling pathways for histamine receptors. Histamine can couple to a variety of G-protein-linked signal transduction pathways via its four different receptors. The Hj receptor activates the phosphatidylinositol turnover via Gq/11 proteins. The other receptors either positively (H2 receptor) or negatively (H3 and H4 receptor) regulate adenylyl cyclase activity via Gs and GUo protein activation respectively. Several additional signaling pathways have been described, which are not shown. Abbreviations PfP2, phosphatidylinositol 4,5-bisphosphate PIC, phospholipase C AC, adenylyl cyclase ATP, adenosine triphosphate cAMP, cyclic AMP PKC, protein kinase C PICA, protein kinase A. 

Adenylyl cyclase in learning and memory. The cAMP-signal transduction cascade has been demonstrated to play a role critical to the formation of long-term memory in both cellular models and in animals. The specific adenylyl cyclases involved are being identified by current research. In AC1 mutant mice there is a partial disruption of long-term potentiation (LTP), a cellular model of... 

Fig. 3. Signal transduction of the tt2A-D79N adrenergic receptor. Mutation of the aspartic acid residue 79 in the second transmembrane domain of the mouse a2A adrenergic receptor to asparagine (D79N) selectively uncoupled this receptor mutant from activation of currents in vitro without interfering with Ca channel or adenylyl cyclase inhibition (Surprenant et al. 1992). In vivo, the a2A D79N receptor was expressed at 20% of the level of the wild-type a2A-receptor (MacMillan et d. 1996), and Ca channel inhibition was also blunted (a) (Lakhlani et al. 1997)...

All muscarinic receptors are members of the seven transmembrane domain, G protein-coupled receptors, and they are structurally and functionally unrelated to nicotinic ACh receptors. Activation of muscarinic receptors by an agonist triggers the release of an intracellular G-protein complex that can specifically activate one or more signal transduction pathways. Fortunately, the cellular responses elicited by odd- versus even-numbered receptor subtypes can be conveniently distinguished. Activation of Ml, M3, and M5 receptors produces an inosine triphosphate (IP3) mediated release of intracellular calcium, the release of diacylglyc-erol (which can activate protein kinase C), and stimulation of adenylyl cyclase. These receptors are primarily responsible for activating calcium-dependent responses, such as secretion by glands and the contraction of smooth muscle. 

Despite the central importance of adenylyl cyclase for hormonal signal transduction, its structural and functional characterization is incomplete. In mammals, at least 9 dif-... 

FIGURE 12-12 Transduction of the epinephrine signal the /J-adrenergic pathway. The seven steps of the mechanism that couples binding of epinephrine (E) to its receptor (Rec) with activation of adenylyl cyclase (AC) are discussed further in the text. The same adenylyl cyclase molecule in the plasma membrane may be regulated by a stimulatory G protein (Gs), as shown, or an inhibitory G protein (G, not shown). Gs and G, are under the influence of different hormones. Hormones that induce GTP binding to G, cause inhibition of adenylyl cyclase, resulting in lower cellular [cAMP]. 

Signal transduction by adenylyl cyclase entails several steps that amplify the original hormone signal (Fig. 

Some olfactory neurons may use a second transduction mechanism. They have receptors coupled through G proteins to PLC rather than to adenylyl cyclase. Signal reception in these cells triggers production of IP3 (Fig. 12-19), which opens IP3-gated Ca2+ channels in the ciliary membrane. Influx of Ca2+ then depolarizes the ciliary membrane and generates a receptor potential or regulates Ca2+-dependent enzymes in the olfactory pathway. 

A number of cardiovascular disease states that eventually result in chronic congestive heart failure are associated with alterations in cardiac performance. Several hormonal factors such as angiotensin II, endothelin, and alterations in signal transduction mechanisms including adenylyl cyclase and phospholipase C (PLC) have been reported to play an important role in the alterations of cardiac performance. 

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