Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular System

Ercu, Maria; Klussmann, Enno

doi:10.3390/jcdd5010014

Cited by 40 publications

(45 citation statements)

References 204 publications

(270 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Compartmentation is also essential to pick the correct target for phosphorylation. For protein kinase A – the closest homolog of cGKI - a number of AKAPs (for A k inase a nchoring p roteins) have been characterized which immobilize PKA into scaffolds of signaling complexes containing activators and substrates which are phosphorylated by PKA ( Torres-Quesada et al, 2017 ; Ercu and Klussmann, 2018 ). cGKI is expressed as two isoforms, termed α and β, that differ in their first ∼100 N-terminal residues.…”

Section: Discussionmentioning

confidence: 99%

S-palmitoylation Is Required for the Control of Growth Cone Morphology of DRG Neurons by CNP-Induced cGMP Signaling

Dumoulin

Dagane

Dittmar

et al. 2018

Front. Mol. Neurosci.

View full text Add to dashboard Cite

Genetic investigations have demonstrated that a specific form of axonal branching - the bifurcation of afferents from dorsal root ganglia (DRG), cranial sensory ganglia (CSG) and mesencephalic trigeminal neurons (MTN) – is regulated by a cGMP-dependent signaling pathway. This cascade is composed of the ligand C-type natriuretic peptide (CNP), the receptor guanylyl cyclase Npr2, and the cGMP-dependent protein kinase Iα (cGKIα). In the absence of any one of these components, axons no longer bifurcate, instead they turn in either an ascending or a descending direction. To gain further mechanistic insights into the process of axon bifurcation we applied different cell culture approaches to decipher downstream activities of cGKI in somatosensory growth cones. We demonstrate that CNP induces an enlargement of DRG growth cones via cGKI which is considered as the priming step of axon bifurcation in the spinal cord. This growth cone remodeling was both blocked by pharmacological inhibitors of S-palmitoylation and potentiated by blocking de-palmitoylation. cGKI colocalizes with the palmitoylome and vesicular structures including the endoplasmic reticulum, early endosomes, lysosomes primarily in the central domain of the growth cone as well as with the Golgi apparatus at the level of the soma. Interestingly, an acyl-biotin-exchange chemistry-based screen indicated that 8pCPT-cGMP-induced signaling induces S-palmitoylation of a restricted pool of proteins in the DRG-derived cell line F11. Overall, our data indicate that CNP-induced cGMP signaling via cGKI affects growth cone morphology of somatosensory afferents. Moreover, it also suggests that S-palmitoylation might play a role in this process.

show abstract

Section: Discussionmentioning

confidence: 99%

S-palmitoylation Is Required for the Control of Growth Cone Morphology of DRG Neurons by CNP-Induced cGMP Signaling

Dumoulin

Dagane

Dittmar

et al. 2018

Front. Mol. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Secondly, compartmentalization of PDEs further contributes in shaping cAMP microdomains by defining molecular barriers for cAMP diffusion [30,32]. Thirdly, organization of macromolecular signaling complexes containing ACs, PDEs, PKA, and its physiological substrates by a family of scaffolding proteins named A-kinase anchoring proteins (AKAPs), ensures spatiotemporal regulation of cAMP signaling events [31,33,34].…”

Section: The Functional Role Of Camp Signaling In Cardiac Fibroblastsmentioning

confidence: 99%

“…In the heart, AKAPs have been shown to regulate multiple physiological responses including cardiac contraction, rhythm and energy production as well as pathological functions linked to the development of arrhythmias, cardiac hypertrophy, fibrosis, and heart failure [7,141,142]. Several studies indicate that altering AKAP expression and signaling in cardiomyocytes can significantly impact their ability to survive cardiac stress and consequently influence replacement fibrosis [33,140,[143][144][145]. Since these results have been extensively reviewed in recent years, in the next paragraphs we will mainly focus on recent findings highlighting the role of AKAP signaling in cardiac fibroblasts.…”

Section: A-kinase Anchoring Proteinsmentioning

confidence: 99%

The Role of Cyclic AMP Signaling in Cardiac Fibrosis

Delaunay

Osman

Kaiser

et al. 2019

Cells

View full text Add to dashboard Cite

Myocardial stress and injury invariably promote remodeling of the cardiac tissue, which is associated with cardiomyocyte death and development of fibrosis. The fibrotic process is initially triggered by the differentiation of resident cardiac fibroblasts into myofibroblasts. These activated fibroblasts display increased proliferative capacity and secrete large amounts of extracellular matrix. Uncontrolled myofibroblast activation can thus promote heart stiffness, cardiac dysfunction, arrhythmias, and progression to heart failure. Despite the well-established role of myofibroblasts in mediating cardiac disease, our current knowledge on how signaling pathways promoting fibrosis are regulated and coordinated in this cell type is largely incomplete. In this respect, cyclic adenosine monophosphate (cAMP) signaling acts as a major modulator of fibrotic responses activated in fibroblasts of injured or stressed hearts. In particular, accumulating evidence now suggests that upstream cAMP modulators including G protein-coupled receptors, adenylyl cyclases (ACs), and phosphodiesterases (PDEs); downstream cAMP effectors such as protein kinase A (PKA) and the guanine nucleotide exchange factor Epac; and cAMP signaling organizers such as A-kinase anchoring proteins (AKAPs) modulate a variety of fundamental cellular processes involved in myocardial fibrosis including myofibroblast differentiation, proliferation, collagen secretion, and invasiveness. The current review will discuss recent advances highlighting the role of cAMP and AKAP-mediated signaling in regulating pathophysiological responses controlling cardiac fibrosis.

show abstract

“…AKAPs are distinguished by their ability to bind cyclic adenosine monophosphate (cAMP)‐PKA at focal points within the cell to ensure the integration and processing of multiple signalling pathways . AKAP150 is an AKAP5 gene product that was first identified as a scaffolding protein predominantly expressed in the cerebral cortex that anchored the RII regulatory subunit of PKA to post‐synaptic densities . However, abundant data have shown that AKAP150 is important in the nervous system in functions such as neuron excitability and neuroendocrine function .…”

Section: Discussionmentioning

confidence: 99%

Knockout of AKAP150 improves impaired BK channel‐mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus

Zhu

Jiang

et al. 2020

J Cellular Molecular Medi

View full text Add to dashboard Cite

Type 1 diabetes mellitus is characterized by the destruction of pancreatic beta cells mediated by the immune system, resulting in reduced insulin secretion and lifelong dependence on exogenous insulin. 1 Diabetes is an independent risk factor for vascular complications (such as atherosclerosis of the coronary artery and stroke) and a main cause of the prevalence and mortality of cardiovascular diseases. 2,3 Vascular dysfunction results from a chronic hyperglycaemic state, which leads to increased oxidative stress, AbstractVascular dysfunction resulting from diabetes is an important factor in arteriosclerosis. Previous studies have shown that during hyperglycaemia and diabetes, AKAP150 promotes vascular tone enhancement by intensifying the remodelling of the BK channel. However, the interaction between AKAP150 and the BK channel remains open to discussion. In this study, we investigated the regulation of impaired BK channel-mediated vascular dysfunction in diabetes mellitus. Using AKAP150 null mice (AKAP150 −/− ) and wild-type (WT) control mice (C57BL/6J), diabetes was induced by intraperitoneal injection of streptozotocin. We found that knockout of AKAP150 reversed vascular remodelling and fibrosis in mice with diabetes and in AKAP150 −/− diabetic mice. Impaired Akt/GSK3β signalling contributed to decreased BK-β 1 expression in aortas from diabetic mice, and the silencing of AKAP150 increased Akt phosphorylation and BK-β 1 expression in MOVAS cells treated with HG medium. The inhibition of Akt activity caused a decrease in BK-β 1 expression, and treatment with AKAP150 siRNA suppressed GSK3β expression in the nuclei of MOVAS cells treated with HG. Knockout of AKAP150 reverses impaired BK channel-mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus. K E Y W O R D SA-kinase anchoring protein, diabetes mellitus, the large-conductance Ca 2+ -activated K + channel, vascular diseases, vascular smooth muscle cells | 4717 ZHU et al.

show abstract

Roles of A-Kinase Anchoring Proteins and Phosphodiesterases in the Cardiovascular System

Cited by 40 publications

References 204 publications

S-palmitoylation Is Required for the Control of Growth Cone Morphology of DRG Neurons by CNP-Induced cGMP Signaling

S-palmitoylation Is Required for the Control of Growth Cone Morphology of DRG Neurons by CNP-Induced cGMP Signaling

The Role of Cyclic AMP Signaling in Cardiac Fibrosis

Knockout of AKAP150 improves impaired BK channel‐mediated vascular dysfunction through the Akt/GSK3β signalling pathway in diabetes mellitus

Contact Info

Product

Resources

About