Compartmentalization of cyclic nucleotide signaling: a question of when, where, and why?

Abstract

Preciseness of cellular behavior depends upon how an extracellular cue mobilizes a correct orchestra of cellular messengers and effector proteins spatially and temporally. This concept, termed compartmentalization of cellular signaling, is now known to form the molecular basis of many aspects of cellular behavior in health and disease. The cyclic nucleotides cAMP and cGMP are ubiquitous cellular messengers that can be compartmentalized in three ways: first, by their physical containment; second, by formation of multiple protein signaling complexes; and third, by their selective depletion. Compartmentalized cyclic nucleotide signaling is a very prevalent response among all cell types. In order to understand how it becomes relevant to cellular behavior, it is important to know how it is executed in cells to regulate physiological responses and, also, how its execution or dysregulation can lead to a pathophysiological condition, which forms the current scope of the presented review.

Modulation of cGMP accumulation by adenosine A1 receptors at the hippocampus: Influence of cGMP levels and gender

“…(see Arora et al, 2013). Therefore, in the present study, we used experimental conditions that would prevent cGMP degradation and induce maximal cGMP accumulation.…”

MRP4-Dependent Regulation of Fibroblast Migration

“…In recent years increasing evidences are suggesting that the cyclic nucleotidedependent signalings are highly compartmentalized (24,25). Being a membrane protein, MRP4 plays a critical role in regulating the compartmentalized cyclic nucleotides near or at the plasma membrane.…”

“…The diversity of PDE isoforms ensure characteristic cyclic nucleotide dependent signaling in diverse cell or tissue types. Their subcellular localization and specific association with effector and adaptor proteins also determine the compartmentalization of signaling events involving cAMP and cGMP (24,38). Endogenous efflux transporters of cAMP and cGMP (MRP4 and MRP5) play pivotal roles in this aspect.…”

“…An altered cyclic nucleotide signaling is often associated with pathological conditions like cancer, fibrotic diseases, metabolic diseases, neuronal disorders and defective immune response. (20,24,37,38). These simple but elegant molecules carry the external signals inside the cell as secondary messengers.…”

“…These simple but elegant molecules carry the external signals inside the cell as secondary messengers. Depending on the cell types, cell environment, localization and intensity of signal, they can elicit different intracellular events in response to the same external cue (24).…”