Abstract
Mounting evidence confirms the compartmentalized structure of evolutionarily conserved 3′–5′-cyclic adenosine monophosphate (cAMP) signaling, which allows for simultaneous participation in a wide variety of physiological functions and ensures specificity, selectivity and signal strength. One important player in cAMP signaling is soluble adenylyl cyclase (sAC). The intracellular localization of sAC allows for the formation of unique intracellular cAMP microdomains that control various physiological and pathological processes. This review is focused on the functional role of sAC-produced cAMP. In particular, we examine the role of sAC-cAMP in different cellular compartments, such as cytosol, nucleus and mitochondria.
Highlights
Even though 3 –5 -cyclic adenosine monophosphate was discovered more than half a century ago, it still remains an object of scientific interest. cAMP signaling plays an important role in a wide variety of physiological processes: transcription regulation [1,2], metabolism [3,4], cell migration [5,6], mitochondrial homeostasis [7,8,9,10,11], as well as cell proliferation [13] and cell death [15]
Conclusions cAMP signaling plays a fundamental role in controlling numerous cellular functions
Different mechanisms are involved in the compartmentalized structure of cAMP within the cell, including phosphodiesterases, tmACand soluble adenylyl cyclases (sAC)-dependent cAMP sources
Summary
Even though 3 –5 -cyclic adenosine monophosphate (cAMP) was discovered more than half a century ago, it still remains an object of scientific interest. cAMP signaling plays an important role in a wide variety of physiological processes: transcription regulation [1,2], metabolism [3,4], cell migration [5,6], mitochondrial homeostasis [7,8,9,10,11] (reviewed in Reference [12]), as well as cell proliferation [13] (reviewed in Reference [14]) and cell death [15] (reviewed in Reference [16]). CAMP signaling plays an important role in a wide variety of physiological processes: transcription regulation [1,2], metabolism [3,4], cell migration [5,6], mitochondrial homeostasis [7,8,9,10,11] (reviewed in Reference [12]), as well as cell proliferation [13] (reviewed in Reference [14]) and cell death [15] (reviewed in Reference [16]). There are two main sources of cAMP in the cell: Transmembrane (tmAC) and intracellularly localized soluble adenylyl cyclases (sAC). Two important properties characterize the principal difference between tmAC and sAC: First, Gs, Gi, Gαi/o, Gßγ and Gq proteins regulate tmAC activity [22,23], whereas sAC activity is regulated by bicarbonate [24]; second, tmAC’s localization is restricted to the plasma membrane, while sAC is widely distributed within the cell and organelles [25]. We focus on sAC-dependent cAMP signaling, with a particular focus on its role in mitochondrial biology
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