scholarly journals GABA induces the differentiation of small into large cholangiocytes by activation of Ca2+/CaMK I-dependent adenylyl cyclase 8

Hepatology ◽  
2013 ◽  
Vol 58 (1) ◽  
pp. 251-263 ◽  
Author(s):  
Romina Mancinelli ◽  
Antonio Franchitto ◽  
Shannon Glaser ◽  
Fanyin Meng ◽  
Paolo Onori ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Adenylyl Cyclase 8

scholarly journals Identification of FDA-Approved Small Molecules Capable of Disrupting the Calmodulin–Adenylyl Cyclase 8 Interaction through Direct Binding to Calmodulin

2017 ◽  
Vol 9 (2) ◽  
pp. 346-357 ◽  
Author(s):  
Michael P. Hayes ◽  
Monica Soto-Velasquez ◽  
C. Andrew Fowler ◽  
Val J. Watts ◽  
David L. Roman
Keyword(s):  
Small Molecules ◽  
Adenylyl Cyclase ◽  
Direct Binding ◽  
Adenylyl Cyclase 8

scholarly journals Calcium influx activates adenylyl cyclase 8 for sustained insulin secretion in rat pancreatic beta cells

Diabetologia ◽  
2014 ◽  
Vol 58 (2) ◽  
pp. 324-333 ◽  
Author(s):  
Haiqiang Dou ◽  
Changhe Wang ◽  
Xi Wu ◽  
Lijun Yao ◽  
Xiaoyu Zhang ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Adenylyl Cyclase ◽  
Beta Cells ◽  
Pancreatic Beta Cells ◽  
Calcium Influx ◽  
Adenylyl Cyclase 8

Implication of adenylyl cyclase 8 in pathological smooth muscle cell migration occurring in rat and human vascular remodelling

2010 ◽  
Vol 221 (3) ◽  
pp. 331-342 ◽  
Author(s):  
Marie Gueguen ◽  
Zela Keuylian ◽  
Véronique Mateo ◽  
Nathalie Mougenot ◽  
Anne-Marie Lompré ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Cell Migration ◽  
Smooth Muscle Cell ◽  
Adenylyl Cyclase ◽  
Muscle Cell ◽  
Vascular Remodelling ◽  
Smooth Muscle Cell Migration ◽  
Adenylyl Cyclase 8

scholarly journals Insights into the residence in lipid rafts of adenylyl cyclase AC8 and its regulation by capacitative calcium entry

2009 ◽  
Vol 296 (3) ◽  
pp. C607-C619 ◽  
Author(s):  
Mario Pagano ◽  
Michael A. Clynes ◽  
Nanako Masada ◽  
Antonio Ciruela ◽  
Laura-Jo Ayling ◽  
...  
Keyword(s):  
Adenylyl Cyclase ◽  
Lipid Rafts ◽  
Leucine Zipper ◽  
Site Directed Mutagenesis ◽  
Directed Mutagenesis ◽  
Adenylyl Cyclases ◽  
Leucine Zipper Motif ◽  
Capacitative Calcium Entry ◽  
Lipid Raft Microdomains ◽  
Adenylyl Cyclase 8

Adenylyl cyclases (ACs) are a family of critically important signaling molecules that are regulated by multiple pathways. Adenylyl cyclase 8 (AC8) is a Ca2+ stimulated isoform that displays a selective regulation by capacitative Ca2+ entry (CCE), the process whereby the entry of Ca2+ into cells is triggered by the emptying of intracellular stores. This selectivity was believed to be achieved through the localization of AC8 in lipid raft microdomains, along with components of the CCE apparatus. In the present study, we show that an intact leucine zipper motif is required for the efficient N-linked glycosylation of AC8, and that this N-linked glycosylation is important to target AC8 into lipid rafts. Disruption of the leucine zipper by site-directed mutagenesis results in the elimination of N-glycosylated forms and their exclusion from lipid rafts. Mutants of AC8 that cannot be N-glycosylated are not demonstrably associated with rafts, although they can still be regulated by CCE; however, raft integrity is required for the regulation of these mutants. These findings suggest that raft localized proteins in addition to AC8 are needed to mediate its regulation by CCE.

scholarly journals AKAP79 Orchestrates a Cyclic AMP Signalosome Adjacent to Orai1 Ca2+ Channels

Function ◽  
2021 ◽  
Author(s):  
Pulak Kar ◽  
Pradeep Barak ◽  
Anna Zerio ◽  
Yu-Ping Lin ◽  
Amy J Parekh ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Kinase A ◽  
Adenylyl Cyclase ◽  
Second Messengers ◽  
Neuronal Cell ◽  
Hek293 Cells ◽  
Scaffolding Protein ◽  
Adenylyl Cyclase 8 ◽  
Ca2 Channels ◽  
Kinase A

Abstract To avoid conflicting and deleterious outcomes, eukaryotic cells often confine signalling molecules to spatially restricted sub-compartments. The smallest signalling unit is the Ca2+ nanodomain, forming near open Ca2+ channels. Ca2+ nanodomains near store-operated Orai1 channels stimulate calcineurin, which activates the transcription factor NFAT1, and both enzyme and target are initially attached to the plasma membrane through the scaffolding protein AKAP79. Here we show that a cAMP signalling nexus also forms adjacent to Orai1. Protein kinase A and phosphodiesterase 4, an enzyme that rapidly breaks down cAMP, both associate with AKAP79 and realign close to Orai1 after stimulation. PCR and mass spectrometry failed to show expression of Ca2+-activated adenylyl cyclase 8 in HEK293 cells, whereas the enzyme was observed in neuronal cell lines. FRET and biochemical measurements of bulk cAMP and protein kinase A activity consistently failed to show an increase in adenylyl cyclase activity following even a large rise in cytosolic Ca2+. Furthermore, expression of AKAP79-CUTie, a cAMP FRET sensor tethered to AKAP79, did not report a rise in cAMP after stimulation, despite AKAP79 association with Orai1. Hence HEK293 cells do not express functionally active Ca2+-activated adenylyl cyclases including adenylyl cyclase 8. Our results show that two ancient second messengers are independently generated in nanodomains close to Orai1 Ca2+ channels.

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