Limits...
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.


Spatiotemporal dynamics of cAMP during neuronal polarization and neurotransmitter specification. (A) Local interactions between cAMP and cGMP determine neurite maturation into axon or dendrite. High cAMP and low cGMP concentrations promote axonogenesis, whereas low cAMP and high cGMP lead to dentritogenesis. (B) In developing neurons, cAMP transients and calcium spikes are interdependent. The choice of expression of excitatory or an inhibitory neurotransmitter is modulated by the frequency of calcium spikes, which is regulated by the activity of a set of kinases including the cAMP effector PKA.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4230202&req=5

Figure 2: Spatiotemporal dynamics of cAMP during neuronal polarization and neurotransmitter specification. (A) Local interactions between cAMP and cGMP determine neurite maturation into axon or dendrite. High cAMP and low cGMP concentrations promote axonogenesis, whereas low cAMP and high cGMP lead to dentritogenesis. (B) In developing neurons, cAMP transients and calcium spikes are interdependent. The choice of expression of excitatory or an inhibitory neurotransmitter is modulated by the frequency of calcium spikes, which is regulated by the activity of a set of kinases including the cAMP effector PKA.

Mentions: The polarization of postmitotic neurons leads to the segregation of two distinct subcellular compartments: a single axon and a somato-dendritic compartment including multiple dendrites (Arimura and Kaibuchi, 2007; Barnes et al., 2008). Axon/dendrite specification of undifferentiated neurites involves cyclic nucleotide signaling aiming at the development of a single axon in each neuron. The use of cAMP and cGMP reporters enabled the identification of local cyclic nucleotide signals regulating axon/dendrite specification. cAMP initiates a positive feedback involving phosphorylation of the serine/threonine kinase LKB1 (Liver Kinase B1) and its interactor STRAD (STE20-related adapter protein), leading to differentiation and stabilization of the axon (Shelly et al., 2007). In contrast, cGMP favors the differentiation of immature neurites into mature dentrites (Shelly et al., 2010). Local and distal interactions between these two second messengers create two subcellular compartments that define the polarity of the neuron. Local cAMP elevation at the tip of a neurite leads to a local reduction of cGMP concentration, and a distal cAMP suppression and cGMP elevation in the other neurites and vice versa (Shelly et al., 2010; Figure 2). This local modulation of cyclic nucleotide levels is observed in maturing neurons in response to extracellular cues that favor either axon or dendrite initiation like BDNF or Semaphorin3A respectively (Shelly et al., 2011), or by activation of GABAB receptors (Bony et al., 2013). These observations emphasize the influence of local cyclic nucleotide signaling for axono- and dendritogenesis.


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

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

Spatiotemporal dynamics of cAMP during neuronal polarization and neurotransmitter specification. (A) Local interactions between cAMP and cGMP determine neurite maturation into axon or dendrite. High cAMP and low cGMP concentrations promote axonogenesis, whereas low cAMP and high cGMP lead to dentritogenesis. (B) In developing neurons, cAMP transients and calcium spikes are interdependent. The choice of expression of excitatory or an inhibitory neurotransmitter is modulated by the frequency of calcium spikes, which is regulated by the activity of a set of kinases including the cAMP effector PKA.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Spatiotemporal dynamics of cAMP during neuronal polarization and neurotransmitter specification. (A) Local interactions between cAMP and cGMP determine neurite maturation into axon or dendrite. High cAMP and low cGMP concentrations promote axonogenesis, whereas low cAMP and high cGMP lead to dentritogenesis. (B) In developing neurons, cAMP transients and calcium spikes are interdependent. The choice of expression of excitatory or an inhibitory neurotransmitter is modulated by the frequency of calcium spikes, which is regulated by the activity of a set of kinases including the cAMP effector PKA.
Mentions: The polarization of postmitotic neurons leads to the segregation of two distinct subcellular compartments: a single axon and a somato-dendritic compartment including multiple dendrites (Arimura and Kaibuchi, 2007; Barnes et al., 2008). Axon/dendrite specification of undifferentiated neurites involves cyclic nucleotide signaling aiming at the development of a single axon in each neuron. The use of cAMP and cGMP reporters enabled the identification of local cyclic nucleotide signals regulating axon/dendrite specification. cAMP initiates a positive feedback involving phosphorylation of the serine/threonine kinase LKB1 (Liver Kinase B1) and its interactor STRAD (STE20-related adapter protein), leading to differentiation and stabilization of the axon (Shelly et al., 2007). In contrast, cGMP favors the differentiation of immature neurites into mature dentrites (Shelly et al., 2010). Local and distal interactions between these two second messengers create two subcellular compartments that define the polarity of the neuron. Local cAMP elevation at the tip of a neurite leads to a local reduction of cGMP concentration, and a distal cAMP suppression and cGMP elevation in the other neurites and vice versa (Shelly et al., 2010; Figure 2). This local modulation of cyclic nucleotide levels is observed in maturing neurons in response to extracellular cues that favor either axon or dendrite initiation like BDNF or Semaphorin3A respectively (Shelly et al., 2011), or by activation of GABAB receptors (Bony et al., 2013). These observations emphasize the influence of local cyclic nucleotide signaling for axono- and dendritogenesis.

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.