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Compound
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Target Concepts:
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Query: EC:4.6.1.1 (
adenylate cyclase
)
19,190
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Airway epithelial cells express both Ca
2+
activated TMEM16A/
ANO1
and cAMP activated CFTR anion channels. Previous work suggested a significant crosstalk of intracellular Ca
2+
and cAMP signaling pathways, leading to activation of both chloride channels. We demonstrate that in airway epithelial cells, stimulation of purinergic or muscarinic G-protein coupled receptors (GPCRs) activates TMEM16A and CFTR. Additional expression of G
q/11
and phospholipase C coupled GPCRs strongly enhanced the crosstalk between Ca
2+
- and cAMP-dependent signaling. Knockdown of endogenous GRCRs attenuated crosstalk and functional coupling between TMEM16A and CFTR. The number of receptors did not affect expression or membrane localization of TMEM16A or CFTR, but controlled assembly of the local signalosome. GPCRs translocate Ca
2+
-sensitive
adenylate cyclase
type 1 (ADCY1) and exchange protein directly activated by cAMP (EPAC1) to particular plasma membrane domains containing GPCRs, CFTR and TMEM16A, thereby producing compartmentalized Ca
2+
and cAMP signals and significant crosstalk. While biosynthesis and membrane trafficking of CFTR requires a functional Golgi apparatus, maturation and membrane trafficking of TMEM16A may occur independent of the Golgi. Because Ca
2+
activated TMEM16A currents are only transient, continuous Cl
-
secretion by airway epithelial cells requires CFTR. The present data also explain why receptor-dependent activation of TMEM16A is more efficient than direct stimulation by Ca
2+
.
...
PMID:Compartmentalized crosstalk of CFTR and TMEM16A (ANO1) through EPAC1 and ADCY1. 2933 8
Anoctamins (ANOs) are multifunctional membrane proteins that consist of 10 homologs.
ANO1
(TMEM16A) and ANO2 (TMEM16B) are anion channels activated by intracellular calcium that meditate numerous physiological functions. ANO6 is a scramblase that redistributes phospholipids across the cell membrane. The other homologs are not well characterized. We found ANO9/TMEM16J is a cation channel activated by a cAMP-dependent protein kinase A (PKA). Intracellular cAMP-activated robust currents in whole cells expressing ANO9, which were inhibited by a PKA blocker. A cholera toxin that persistently stimulated
adenylate cyclase
activated ANO9 as did the application of PKA. The cAMP-induced ANO9 currents were permeable to cations. The cAMP-dependent ANO9 currents were augmented by intracellular Ca
2+
. Ano9 transcripts were predominant in the intestines. Human intestinal SW480 cells expressed high levels of Ano9 transcripts and showed PKA inhibitor-reversible cAMP-dependent currents. We conclude that ANO9 is a cation channel activated by a cAMP/PKA pathway and could play a role in intestine function.
...
PMID:Anoctamin 9/TMEM16J is a cation channel activated by cAMP/PKA signal. 2960 66
