scholarly journals Regulation of type I adenylyl cyclase by calmodulin kinase IV in vivo.

1996 ◽  
Vol 16 (11) ◽  
pp. 6075-6082 ◽  
Author(s):  
G A Wayman ◽  
J Wei ◽  
S Wong ◽  
D R Storm
Keyword(s):  
Adenylyl Cyclase ◽  
Long Term Potentiation ◽  
Type I ◽  
Cam Kinase ◽  
Regulatory Systems ◽  
Calmodulin Kinase ◽  
Term Potentiation ◽  
G Protein Coupled ◽  
Cam Kinase Iv

Type I adenylyl cyclase is a neurospecific enzyme that is stimulated by Ca2+ and calmodulin (CaM). This enzyme couples the Ca2+ and cyclic AMP (cAMP) regulatory systems in neurons, and it may play an important role for some forms of synaptic plasticity. Mutant mice lacking type I adenylyl cyclase show deficiencies in spatial memory and altered long-term potentiation (Z. Wu, S. A. Thomas, Z. Xia, E. C. Villacres, R. D. Palmiter, and D. R. Storm, Proc. Natl. Acad. Sci. USA 92:220-224, 1995). Although type I adenylyl cyclase is synergistically stimulated by Ca2+ and G-protein-coupled receptors in vivo, very little is known about mechanisms for inhibition of the enzyme. Here, we report that type I adenylyl cyclase is inhibited by CaM kinase IV in vivo. Expression of constitutively active or wild-type CaM kinase IV inhibited Ca2+ stimulation of adenylyl cyclase activity without affecting basal or forskolin-stimulated activity. Type I adenylyl cyclase has two CaM kinase IV consensus phosphorylation sequences near its CaM binding domain at Ser-545 and Ser-552. Conversion of either serine to alanine by mutagenesis abolished CaM kinase IV inhibition of adenylyl cyclase. This suggests that the activity of this enzyme may be directly inhibited by CaM kinase IV phosphorylation. Type VIII adenylyl cyclase, another enzyme stimulated by CaM, was not inhibited by CaM kinase II or IV. We propose that CaM kinase IV may function as a negative feedback regulator of type I adenylyl cyclase and that CaM kinases may regulate cAMP levels in some cells.

Type I adenylyl cyclase functions as a coincidence detector for control of cyclic AMP response element-mediated transcription: synergistic regulation of transcription by Ca2+ and isoproterenol

1994 ◽  
Vol 14 (12) ◽  
pp. 8272-8281
Author(s):  
S Impey ◽  
G Wayman ◽  
Z Wu ◽  
D R Storm
Keyword(s):  
Cyclic Amp ◽  
Adenylyl Cyclase ◽  
Long Term Potentiation ◽  
Regulation Of Transcription ◽  
Type I ◽  
Hek 293 ◽  
293 Cells ◽  
Term Potentiation ◽  
Stimulation Of

Studies carried out with mammals and invertebrates suggest that Ca(2+)-sensitive adenylyl cyclases may be important for neuroplasticity. Long-term potentiation in the hippocampus requires increases in intracellular Ca2+ which are accompanied by elevated cyclic AMP (cAMP). Furthermore, activation of cAMP-dependent protein kinase is required for the late stage of long-term potentiation in the CA1 region of the hippocampus, which is also sensitive to inhibitors of transcription. Therefore, some forms of synaptic plasticity may require coordinate regulation of transcription by Ca2+ and cAMP. In this study, we demonstrate that the expression of type I adenylyl cyclase in HEK-293 cells allows Ca2+ to stimulate reporter gene activity mediated through the cAMP response element. Furthermore, simultaneous activation by Ca2+ and isoproterenol caused synergistic stimulation of transcription in HEK-293 cells and cultured neurons. We propose that Ca2+ and neurotransmitter stimulation of type I adenylyl cyclase may play a role in synaptic plasticity by generating optimal cAMP signals for regulation of transcription.

scholarly journals Impaired Cerebellar Long-Term Potentiation in Type I Adenylyl Cyclase Mutant Mice

Neuron ◽  
1998 ◽  
Vol 20 (6) ◽  
pp. 1199-1210 ◽  
Author(s):  
Daniel R Storm ◽  
Christian Hansel ◽  
Beth Hacker ◽  
Angèle Parent ◽  
David J Linden
Keyword(s):  
Adenylyl Cyclase ◽  
Long Term Potentiation ◽  
Mutant Mice ◽  
Type I ◽  
Term Potentiation

scholarly journals Altered behavior and long-term potentiation in type I adenylyl cyclase mutant mice.

1995 ◽  
Vol 92 (1) ◽  
pp. 220-224 ◽  
Author(s):  
Z. L. Wu ◽  
S. A. Thomas ◽  
E. C. Villacres ◽  
Z. Xia ◽  
M. L. Simmons ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Long Term Potentiation ◽  
Mutant Mice ◽  
Type I ◽  
Term Potentiation

scholarly journals Type I Adenylyl Cyclase Mutant Mice Have Impaired Mossy Fiber Long-Term Potentiation

1998 ◽  
Vol 18 (9) ◽  
pp. 3186-3194 ◽  
Author(s):  
Enrique C. Villacres ◽  
Scott T. Wong ◽  
Charles Chavkin ◽  
Daniel R. Storm
Keyword(s):  
Adenylyl Cyclase ◽  
Mossy Fiber ◽  
Long Term Potentiation ◽  
Mutant Mice ◽  
Type I ◽  
Term Potentiation

scholarly journals Type I adenylyl cyclase functions as a coincidence detector for control of cyclic AMP response element-mediated transcription: synergistic regulation of transcription by Ca2+ and isoproterenol.

1994 ◽  
Vol 14 (12) ◽  
pp. 8272-8281 ◽  
Author(s):  
S Impey ◽  
G Wayman ◽  
Z Wu ◽  
D R Storm
Keyword(s):  
Cyclic Amp ◽  
Adenylyl Cyclase ◽  
Long Term Potentiation ◽  
Regulation Of Transcription ◽  
Type I ◽  
Hek 293 ◽  
293 Cells ◽  
Term Potentiation ◽  
Stimulation Of

Studies carried out with mammals and invertebrates suggest that Ca(2+)-sensitive adenylyl cyclases may be important for neuroplasticity. Long-term potentiation in the hippocampus requires increases in intracellular Ca2+ which are accompanied by elevated cyclic AMP (cAMP). Furthermore, activation of cAMP-dependent protein kinase is required for the late stage of long-term potentiation in the CA1 region of the hippocampus, which is also sensitive to inhibitors of transcription. Therefore, some forms of synaptic plasticity may require coordinate regulation of transcription by Ca2+ and cAMP. In this study, we demonstrate that the expression of type I adenylyl cyclase in HEK-293 cells allows Ca2+ to stimulate reporter gene activity mediated through the cAMP response element. Furthermore, simultaneous activation by Ca2+ and isoproterenol caused synergistic stimulation of transcription in HEK-293 cells and cultured neurons. We propose that Ca2+ and neurotransmitter stimulation of type I adenylyl cyclase may play a role in synaptic plasticity by generating optimal cAMP signals for regulation of transcription.

Brivaracetam Prevents the Over-expression of Synaptic Vesicle Protein 2A and Rescues the Deficits of Hippocampal Long-term Potentiation In Vivo in Chronic Temporal Lobe Epilepsy Rats

2020 ◽  
Vol 17 (4) ◽  
pp. 354-360 ◽  
Author(s):  
Yu-Xing Ge ◽  
Ying-Ying Lin ◽  
Qian-Qian Bi ◽  
Yu-Juan Chen
Keyword(s):  
Synaptic Plasticity ◽  
Temporal Lobe Epilepsy ◽  
Synaptic Vesicle ◽  
Long Term Potentiation ◽  
Synaptic Dysfunction ◽  
Over Expression ◽  
Term Potentiation ◽  
Synaptic Vesicle Protein 2A

Background: Patients with temporal lobe epilepsy (TLE) usually suffer from cognitive deficits and recurrent seizures. Brivaracetam (BRV) is a novel anti-epileptic drug (AEDs) recently used for the treatment of partial seizures with or without secondary generalization. Different from other AEDs, BRV has some favorable properties on synaptic plasticity. However, the underlying mechanisms remain elusive. Objective: The aim of this study was to explore the neuroprotective mechanism of BRV on synaptic plasticity in experimental TLE rats. Methods: The effect of chronic treatment with BRV (10 mg/kg) was assessed on Pilocarpine induced TLE model through measurement of the field excitatory postsynaptic potentials (fEPSPs) in vivo. Differentially expressed synaptic vesicle protein 2A (SV2A) were identified with immunoblot. Then, fast phosphorylation of synaptosomal-associated protein 25 (SNAP-25) during long-term potentiation (LTP) induction was performed to investigate the potential roles of BRV on synaptic plasticity in the TLE model. Results: An increased level of SV2A accompanied by a depressed LTP in the hippocampus was shown in epileptic rats. Furthermore, BRV treatment continued for more than 30 days improved the over-expression of SV2A and reversed the synaptic dysfunction in epileptic rats. Additionally, BRV treatment alleviates the abnormal SNAP-25 phosphorylation at Ser187 during LTP induction in epileptic ones, which is relevant to the modulation of synaptic vesicles exocytosis and voltagegated calcium channels. Conclusion: BRV treatment ameliorated the over-expression of SV2A in the hippocampus and rescued the synaptic dysfunction in epileptic rats. These results identify the neuroprotective effect of BRV on TLE model.

scholarly journals Aη-α and Aη-β peptides impair LTP ex vivo within the low nanomolar range and impact neuronal activity in vivo

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Maria Mensch ◽  
Jade Dunot ◽  
Sandy M. Yishan ◽  
Samuel S. Harris ◽  
Aline Blistein ◽  
...  
Keyword(s):  
Neuronal Activity ◽  
Ex Vivo ◽  
Long Term Potentiation ◽  
Network Activity ◽  
Strongly Correlated ◽  
App Processing ◽  
Term Potentiation ◽  
Hippocampal Network

Abstract Background Amyloid precursor protein (APP) processing is central to Alzheimer’s disease (AD) etiology. As early cognitive alterations in AD are strongly correlated to abnormal information processing due to increasing synaptic impairment, it is crucial to characterize how peptides generated through APP cleavage modulate synapse function. We previously described a novel APP processing pathway producing η-secretase-derived peptides (Aη) and revealed that Aη–α, the longest form of Aη produced by η-secretase and α-secretase cleavage, impaired hippocampal long-term potentiation (LTP) ex vivo and neuronal activity in vivo. Methods With the intention of going beyond this initial observation, we performed a comprehensive analysis to further characterize the effects of both Aη-α and the shorter Aη-β peptide on hippocampus function using ex vivo field electrophysiology, in vivo multiphoton calcium imaging, and in vivo electrophysiology. Results We demonstrate that both synthetic peptides acutely impair LTP at low nanomolar concentrations ex vivo and reveal the N-terminus to be a primary site of activity. We further show that Aη-β, like Aη–α, inhibits neuronal activity in vivo and provide confirmation of LTP impairment by Aη–α in vivo. Conclusions These results provide novel insights into the functional role of the recently discovered η-secretase-derived products and suggest that Aη peptides represent important, pathophysiologically relevant, modulators of hippocampal network activity, with profound implications for APP-targeting therapeutic strategies in AD.

scholarly journals Synergistic activation of the type I adenylyl cyclase by Ca2+ and Gs-coupled receptors in vivo.

1994 ◽  
Vol 269 (41) ◽  
pp. 25400-25405
Author(s):  
G A Wayman ◽  
S Impey ◽  
Z Wu ◽  
W Kindsvogel ◽  
L Prichard ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Type I ◽  
Synergistic Activation
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