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Intermingled cAMP, cGMP and calcium spatiotemporal dynamics in developing neuronal circuits.

Averaimo S, Nicol X - Front Cell Neurosci (2014)

Bottom Line: It is involved in a wide range of cellular processes that require independent regulation.However, our understanding of how this single second messenger achieves specific modulation of the signaling pathways involved remains incomplete.The subcellular compartmentalization and temporal regulation of cAMP signals have recently been identified as important coding strategies leading to specificity.

View Article: PubMed Central - PubMed

Affiliation: UMR_7210, Centre National de la Recherche Scientifique Paris, France ; UMR_S 968, Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06 Paris, France ; U968, Institut National de la Santé et de la Recherche Médicale Paris, France.

ABSTRACT
cAMP critically modulates the development of neuronal connectivity. It is involved in a wide range of cellular processes that require independent regulation. However, our understanding of how this single second messenger achieves specific modulation of the signaling pathways involved remains incomplete. The subcellular compartmentalization and temporal regulation of cAMP signals have recently been identified as important coding strategies leading to specificity. Dynamic interactions of this cyclic nucleotide with other second messenger including calcium and cGMP are critically involved in the regulation of spatiotemporal control of cAMP. Recent technical improvements of fluorescent sensors facilitate cAMP monitoring, whereas optogenetic tools permit spatial and temporal control of cAMP manipulations, all of which enabled the direct investigation of spatiotemporal characteristics of cAMP modulation in developing neurons. Focusing on neuronal polarization, neurotransmitter specification, axon guidance, and refinement of neuronal connectivity, we summarize herein the recent advances in understanding the features of cAMP signals and their dynamic interactions with calcium and cGMP involved in shaping the nervous system.

No MeSH data available.


Mechanisms underlying the generation of subcellular domains of cAMP. Distinct subcellular localizations of adenylyl cyclases and phosphodiesterases enable the generation of subcellular domains of cAMP. Ca2+-sensitive transmembrane ACs and their regulating Ca2+ channels are restricted to lipid rafts whereas the Ca2+-independent ACs are excluded from this plasma membrane territory. Phosphodiesterases degrade cAMP close to its site of synthesis and limit the diffusion of the signal. The soluble AC is responsible of cAMP synthesis in discrete locations of the cell including the mitochondria and the nucleus.
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Figure 1: Mechanisms underlying the generation of subcellular domains of cAMP. Distinct subcellular localizations of adenylyl cyclases and phosphodiesterases enable the generation of subcellular domains of cAMP. Ca2+-sensitive transmembrane ACs and their regulating Ca2+ channels are restricted to lipid rafts whereas the Ca2+-independent ACs are excluded from this plasma membrane territory. Phosphodiesterases degrade cAMP close to its site of synthesis and limit the diffusion of the signal. The soluble AC is responsible of cAMP synthesis in discrete locations of the cell including the mitochondria and the nucleus.

Mentions: The biological significance of cAMP signals during different steps of neuronal development relies on a tight control of both, their temporal and spatial features. Synthesis of cAMP is dependent on ACs, whereas the hydrolysis of cyclic nucleotides and extinction of the signal relies on phosphodiesterases (PDEs). The diversity of regulation and localization of ACs (10 isoforms) and PDEs (more than 40 isoforms) offers a wide range of combination to shape specific signals in response to distinct stimuli (Omori and Kotera, 2007; Willoughby and Cooper, 2007; Kleppisch, 2009). The cooperation between ACs and PDEs is crucial to control the time of onset of cAMP elevation and to limit the spatial and temporal expansion of the signal, forming the relevant coding strategies controlling specific activation of cAMP downstream effectors (Figure 1).


Intermingled cAMP, cGMP and calcium spatiotemporal dynamics in developing neuronal circuits.

Averaimo S, Nicol X - Front Cell Neurosci (2014)

Mechanisms underlying the generation of subcellular domains of cAMP. Distinct subcellular localizations of adenylyl cyclases and phosphodiesterases enable the generation of subcellular domains of cAMP. Ca2+-sensitive transmembrane ACs and their regulating Ca2+ channels are restricted to lipid rafts whereas the Ca2+-independent ACs are excluded from this plasma membrane territory. Phosphodiesterases degrade cAMP close to its site of synthesis and limit the diffusion of the signal. The soluble AC is responsible of cAMP synthesis in discrete locations of the cell including the mitochondria and the nucleus.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230202&req=5

Figure 1: Mechanisms underlying the generation of subcellular domains of cAMP. Distinct subcellular localizations of adenylyl cyclases and phosphodiesterases enable the generation of subcellular domains of cAMP. Ca2+-sensitive transmembrane ACs and their regulating Ca2+ channels are restricted to lipid rafts whereas the Ca2+-independent ACs are excluded from this plasma membrane territory. Phosphodiesterases degrade cAMP close to its site of synthesis and limit the diffusion of the signal. The soluble AC is responsible of cAMP synthesis in discrete locations of the cell including the mitochondria and the nucleus.
Mentions: The biological significance of cAMP signals during different steps of neuronal development relies on a tight control of both, their temporal and spatial features. Synthesis of cAMP is dependent on ACs, whereas the hydrolysis of cyclic nucleotides and extinction of the signal relies on phosphodiesterases (PDEs). The diversity of regulation and localization of ACs (10 isoforms) and PDEs (more than 40 isoforms) offers a wide range of combination to shape specific signals in response to distinct stimuli (Omori and Kotera, 2007; Willoughby and Cooper, 2007; Kleppisch, 2009). The cooperation between ACs and PDEs is crucial to control the time of onset of cAMP elevation and to limit the spatial and temporal expansion of the signal, forming the relevant coding strategies controlling specific activation of cAMP downstream effectors (Figure 1).

Bottom Line: It is involved in a wide range of cellular processes that require independent regulation.However, our understanding of how this single second messenger achieves specific modulation of the signaling pathways involved remains incomplete.The subcellular compartmentalization and temporal regulation of cAMP signals have recently been identified as important coding strategies leading to specificity.

View Article: PubMed Central - PubMed

Affiliation: UMR_7210, Centre National de la Recherche Scientifique Paris, France ; UMR_S 968, Institut de la Vision, Sorbonne Universités, UPMC Univ Paris 06 Paris, France ; U968, Institut National de la Santé et de la Recherche Médicale Paris, France.

ABSTRACT
cAMP critically modulates the development of neuronal connectivity. It is involved in a wide range of cellular processes that require independent regulation. However, our understanding of how this single second messenger achieves specific modulation of the signaling pathways involved remains incomplete. The subcellular compartmentalization and temporal regulation of cAMP signals have recently been identified as important coding strategies leading to specificity. Dynamic interactions of this cyclic nucleotide with other second messenger including calcium and cGMP are critically involved in the regulation of spatiotemporal control of cAMP. Recent technical improvements of fluorescent sensors facilitate cAMP monitoring, whereas optogenetic tools permit spatial and temporal control of cAMP manipulations, all of which enabled the direct investigation of spatiotemporal characteristics of cAMP modulation in developing neurons. Focusing on neuronal polarization, neurotransmitter specification, axon guidance, and refinement of neuronal connectivity, we summarize herein the recent advances in understanding the features of cAMP signals and their dynamic interactions with calcium and cGMP involved in shaping the nervous system.

No MeSH data available.