Aggregates of cAMP-Dependent Kinase Isoforms Characterize Different Areas in the Developing Central Nervous System of the Chicken, &lt;i&gt;Gallus gallus&lt;/i&gt;

Mucignat‐Caretta, Carla; Caretta, Antonio

doi:10.1159/000329546

Cited by 3 publications

(3 citation statements)

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“…RIA and RIB insoluble clusters are present only in neural cells of some brain areas and appear with a specific developmental time course [5][6][7][8], while RII clusters are widely distributed and are present also 2 of 17 on non-neural cells, for example, glial and ependymal cells, from earlier stages of development [9]. A similar distribution is detected in homolog areas of different species, such as chicken, lizard and turtles [10,11]. PKA regulatory subunits also vary in different human diseases or animal models of disease, including depression, different brain tumors and Parkinson's disease [12][13][14][15][16][17].…”

Section: Introductionmentioning

confidence: 71%

Protein Kinase A Catalytic and Regulatory Subunits Interact Differently in Various Areas of Mouse Brain

Mucignat‐Caretta

Caretta

2020

IJMS

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Protein kinase A (PKA) are tetramers of two catalytic and two regulatory subunits, docked at precise intracellular sites to provide localized phosphorylating activity, triggered by cAMP binding to regulatory subunits and subsequent dissociation of catalytic subunits. It is unclear whether in the brain PKA dissociated subunits may also be found. PKA catalytic subunit was examined in various mouse brain areas using immunofluorescence, equilibrium binding and western blot, to reveal its location in comparison to regulatory subunits type RI and RII. In the cerebral cortex, catalytic subunits colocalized with clusters of RI, yet not all RI clusters were bound to catalytic subunits. In stria terminalis, catalytic subunits were in proximity to RI but separated from them. Catalytic subunits clusters were also present in the corpus striatum, where RII clusters were detected, whereas RI clusters were absent. Upon cAMP addition, the distribution of regulatory subunits did not change, while catalytic subunits were completely released from regulatory subunits. Unpredictably, catalytic subunits were not solubilized; instead, they re-targeted to other binding sites within the tissue, suggesting local macromolecular reorganization. Hence, the interactions between catalytic and regulatory subunits of protein kinase A consistently vary in different brain areas, supporting the idea of multiple interaction patterns.

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Section: Introductionmentioning

confidence: 71%

Protein Kinase A Catalytic and Regulatory Subunits Interact Differently in Various Areas of Mouse Brain

Mucignat‐Caretta

Caretta

2020

IJMS

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“…Regulatory subunits of PKA form homodimers, contributing to the specificity of the signalling system. We described the localization of the docked pool of the regulatory subunits of PKA in the brain of tetrapods, along with the changes that take place during ontogenetic development in the brain of mammals, birds, and reptiles [12,13,14,20,21,22], showing that homolog brain areas present a similar PKA distribution, related to cell type and developmental stage. This distribution may change in animal models of disease, like Parkinson’s disease and depression [23,24].…”

Section: Discussionmentioning

confidence: 99%

Protein Kinase A Distribution in Meningioma

Caretta

Denaro

D’Avella

et al. 2019

Cancers

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Deregulation of intracellular signal transduction pathways is a hallmark of cancer cells, clearly differentiating them from healthy cells. Differential intracellular distribution of the cAMP-dependent protein kinases (PKA) was previously detected in cell cultures and in vivo in glioblastoma and medulloblastoma. Our goal is to extend this observation to meningioma, to explore possible differences among tumors of different origins and prospective outcomes. The distribution of regulatory and catalytic subunits of PKA has been examined in tissue specimens obtained during surgery from meningioma patients. PKA RI subunit appeared more evenly distributed throughout the cytoplasm, but it was clearly detectable only in some tumors. RII was present in discrete spots, presumably at high local concentration; these aggregates could also be visualized under equilibrium binding conditions with fluorescent 8-substituted cAMP analogues, at variance with normal brain tissue and other brain tumors. The PKA catalytic subunit showed exactly overlapping pattern to RII and in fixed sections could be visualized by fluorescent cAMP analogues. Gene expression analysis showed that the PKA catalytic subunit revealed a significant correlation pattern with genes involved in meningioma. Hence, meningioma patients show a distinctive distribution pattern of PKA regulatory and catalytic subunits, different from glioblastoma, medulloblastoma, and healthy brain tissue. These observations raise the possibility of exploiting the PKA intracellular pathway as a diagnostic tool and possible therapeutic interventions.

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“…[ 12 ] These observations are supported by a similar distribution observed in homologue areas of birds and reptiles. [ 13,14 ] To improve brain labeling, we synthesized a new fluorescently tagged cAMP molecule, which was tested in three areas of the mouse brain, to test the efficacy of the new molecule by comparing it with previous findings. A second aim was to highlight possible additional properties of the molecule, for example, improved stability and increased sensitivity, which may represent an advance and suggest it to be a valuable molecular tool for microscopy investigations.…”

Section: Introductionmentioning

confidence: 99%

A new sensitive and subunit‐selective molecular tool for investigating protein kinase A in the brain

Ribaudo

Zagotto

Ongaro

et al. 2020

Archiv der Pharmazie

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Despite cellular complexity, a limited number of small molecules act as intracellular second messengers. Protein kinase A (PKA) is the main transducer of the information carried by cyclic adenosine monophosphate (cAMP). Recently, cellular imaging has achieved major technical advancements, although the search for more specific and sensitive low‐molecular‐weight probes to explore subcellular events involving second messengers is still in progress. The convergent synthesis of a novel, fluorescent small molecule comprising the cAMP structure and a rhodamine‐based fluorescent residue, connected through a flexible linker, is described here. The interaction motif of this compound with PKA was investigated in silico using a blind docking approach, comparing its theoretical binding energy with the one calculated for cAMP. Moreover, the predicted pharmacokinetic properties were also computed and discussed. The new probe was tested on three areas of the mouse central nervous system (parietal cerebral cortex, hippocampus, and cerebellar cortex) with different fixation methods demonstrating remarkable selectivity towards the PKA RIα subunit. The probe showed overall better performances when compared to other commercially available fluorescent cAMP analogues, acting at lower concentrations, and providing stable labeling.

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Aggregates of cAMP-Dependent Kinase Isoforms Characterize Different Areas in the Developing Central Nervous System of the Chicken, <i>Gallus gallus</i>

Cited by 3 publications

References 108 publications

Protein Kinase A Catalytic and Regulatory Subunits Interact Differently in Various Areas of Mouse Brain

Protein Kinase A Catalytic and Regulatory Subunits Interact Differently in Various Areas of Mouse Brain

Protein Kinase A Distribution in Meningioma

A new sensitive and subunit‐selective molecular tool for investigating protein kinase A in the brain

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