Publication details for Professor Martin CannCann, M (2007). A subset of GAF domains are evolutionarily conserved sodium sensors. Molecular Microbiology 64(2): 461-472.
- Publication type: Journal Article
- ISSN/ISBN: 0950-382X, 1365-2958
- DOI: 10.1111/j.1365-2958.2007.05669.x
- Further publication details on publisher web site
- Durham Research Online (DRO) - may include full text
Author(s) from Durham
Most organisms maintain a transmembrane sodium gradient for cell function. Despite the importance of Na+ in physiology, no directly Na+-responsive signalling molecules are known. The CyaB1 and CyaB2 adenylyl cyclases of the cyanobacterium Anabaena PCC 7120 are inhibited by Na+. A D360A mutation in the GAF-B domain of CyaB1 ablated cAMP-mediated autoregulation and Na+ inhibition. Na+ bound the isolated GAF domains of CyaB2. cAMP blocked Na+ binding to GAF domains but Na+ had no effect on cAMP binding. Na+ altered GAF domain structure indicating a mechanism of inhibition independent of cAMP binding. ΔcyaB1 and ΔcyaB2 mutant strains did not grow below 0.6 mM Na+ and ΔcyaB1 cells possessed defects in Na+/H+ antiporter function. Replacement of the CyaB1 GAF domains with those of rat phosphodiesterase type 2 revealed that Na+ inhibition has been conserved since the eukaryotic/bacterial divergence. CyaB1 and CyaB2 are the first identified directly Na+-responsive signalling molecules that function in sodium homeostasis and we propose a subset of GAF domains underpin an evolutionarily conserved Na+ signalling mechanism.