scholarly journals Microglia control the glycinergic but not the GABAergic synapses via prostaglandin E2 in the spinal cord

2017 ◽  
Vol 216 (9) ◽  
pp. 2979-2989 ◽  
Author(s):  
Yasmine Cantaut-Belarif ◽  
Myriam Antri ◽  
Rocco Pizzarelli ◽  
Sabrina Colasse ◽  
Ilaria Vaccari ◽  
...  
Keyword(s):  
Prostaglandin E2 ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Brain Diseases ◽  
Excitatory Synapses ◽  
Diffusion Dynamics ◽  
Gabaergic Synapses ◽  
Dependent Protein ◽  
Activity Dependent ◽  
Early Features

Microglia control excitatory synapses, but their role in inhibitory neurotransmission has been less well characterized. Herein, we show that microglia control the strength of glycinergic but not GABAergic synapses via modulation of the diffusion dynamics and synaptic trapping of glycine (GlyR) but not GABAA receptors. We further demonstrate that microglia regulate the activity-dependent plasticity of glycinergic synapses by tuning the GlyR diffusion trap. This microglia–synapse cross talk requires production of prostaglandin E2 by microglia, leading to the activation of neuronal EP2 receptors and cyclic adenosine monophosphate–dependent protein kinase. Thus, we now provide a link between microglial activation and synaptic dysfunctions, which are common early features of many brain diseases.

scholarly journals PKA-RII subunit phosphorylation precedes activation by cAMP and regulates activity termination

2018 ◽  
Vol 217 (6) ◽  
pp. 2167-2184 ◽  
Author(s):  
Jörg Isensee ◽  
Melanie Kaufholz ◽  
Matthias J. Knape ◽  
Jan Hasenauer ◽  
Hanna Hammerich ◽  
...  
Keyword(s):  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Mechanistic Modeling ◽  
Type Ii ◽  
Dependent Protein Kinase ◽  
Catalytic Subunits ◽  
Dependent Protein ◽  
Inhibitory Domain ◽  
Activity Dependent

Type II isoforms of cyclic adenosine monophosphate (cAMP)–dependent protein kinase A (PKA-II) contain a phosphorylatable epitope within the inhibitory domain of RII subunits (pRII) with still unclear function. In vitro, RII phosphorylation occurs in the absence of cAMP, whereas staining of cells with pRII-specific antibodies revealed a cAMP-dependent pattern. In sensory neurons, we found that increased pRII immunoreactivity reflects increased accessibility of the already phosphorylated RII epitope during cAMP-induced opening of the tetrameric RII2:C2 holoenzyme. Accordingly, induction of pRII by cAMP was sensitive to novel inhibitors of dissociation, whereas blocking catalytic activity was ineffective. Also in vitro, cAMP increased the binding of pRII antibodies to RII2:C2 holoenzymes. Identification of an antibody specific for the glycine-rich loop of catalytic subunits facing the pRII-epitope confirmed activity-dependent binding with similar kinetics, proving that the reassociation is rapid and precisely controlled. Mechanistic modeling further supported that RII phosphorylation precedes cAMP binding and controls the inactivation by modulating the reassociation involving the coordinated action of phosphodiesterases and phosphatases.

scholarly journals Dibutyryl cyclic adenosine monophosphate reduces expression of c-myc during HL-60 differentiation

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 412-416
Author(s):  
SS Jr McCachren ◽  
J Nichols ◽  
RE Kaufman ◽  
JE Niedel
Keyword(s):  
Leukemia Cell ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Mechanisms Of Action ◽  
Promyelocytic Leukemia ◽  
Leukemia Cell Line ◽  
Dependent Protein Kinase ◽  
Rna Transcripts ◽  
Dependent Protein ◽  
Promyelocytic Leukemia Cell Line

The human promyelocytic leukemia cell line HL-60 is induced to differentiate along a myelocytic pathway by dibutyryl cyclic adenosine monophosphate (dbcAMP). Other cAMP analogs are ineffective as inducing agents. The effect of these compounds on expression of c-myc was investigated using a DNA probe for c-myc to detect RNA transcripts. The dose response and time to commitment for reduction in c-myc expression with dbcAMP was similar to the findings for phenotypic changes. Bromo- cyclic AMP and butyrate alone caused no changes in c-myc expression in 24 hours, but demonstrated dramatic synergism together, suggesting that butyrate contributes in part to the effects of dbcAMP. Evidence for mechanisms of action of cAMP other than activation of the cAMP- dependent protein kinase is reviewed.

scholarly journals Dibutyryl cyclic adenosine monophosphate reduces expression of c-myc during HL-60 differentiation

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 412-416 ◽  
Author(s):  
SS Jr McCachren ◽  
J Nichols ◽  
RE Kaufman ◽  
JE Niedel
Keyword(s):  
Leukemia Cell ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Mechanisms Of Action ◽  
Promyelocytic Leukemia ◽  
Leukemia Cell Line ◽  
Dependent Protein Kinase ◽  
Rna Transcripts ◽  
Dependent Protein ◽  
Promyelocytic Leukemia Cell Line

Abstract The human promyelocytic leukemia cell line HL-60 is induced to differentiate along a myelocytic pathway by dibutyryl cyclic adenosine monophosphate (dbcAMP). Other cAMP analogs are ineffective as inducing agents. The effect of these compounds on expression of c-myc was investigated using a DNA probe for c-myc to detect RNA transcripts. The dose response and time to commitment for reduction in c-myc expression with dbcAMP was similar to the findings for phenotypic changes. Bromo- cyclic AMP and butyrate alone caused no changes in c-myc expression in 24 hours, but demonstrated dramatic synergism together, suggesting that butyrate contributes in part to the effects of dbcAMP. Evidence for mechanisms of action of cAMP other than activation of the cAMP- dependent protein kinase is reviewed.

Identification, Characterization, and Hormonal Regulation of 3′,5′-Cyclic Adenosine Monophosphate Dependent Protein Kinases in Rat Sertoli Cells*

Endocrinology ◽  
1991 ◽  
Vol 129 (5) ◽  
pp. 2345-2354 ◽  
Author(s):  
BRYNJAR F. LANDMARK ◽  
BEATHE FAUSKE ◽  
WINNIE ESKILD ◽  
BJØRN SKÅLHEGG ◽  
SUZANNE M. LOHMANN ◽  
...  
Keyword(s):  
Protein Kinases ◽  
Sertoli Cells ◽  
Hormonal Regulation ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Dependent Protein
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