AKAP9/A0009

AKAP9 (A-kinase anchor protein), also known as yotiao or A0009, forms a macromolecular complex with different ion channels and recruits key enzymes such as cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) and protein phosphatase 1

AKAP9 (A-kinase anchor protein), also known as yotiao or A0009, forms a macromolecular complex with different ion channels and recruits key enzymes such as cyclic adenosine monophosphate (cAMP)-dependent protein kinase A (PKA) and protein phosphatase 1 (PP1) to control the phosphorylation state of ion channels such as the I(Ks) potassium channel. This protein binds to subunits of PKA, targeting the enzyme near the substrate and producing compartmentalization of cAMP signaling. The interaction of AKAP9 with I(Ks) potassium channels is important in the regulation of the stimulation of the sympathetic nervous system in cardiac action potential. Additionally, AKAP9 regulates ion channel activity. This protein is expressed in the brain but also in most tissues tested, with highest levels in the kidney. In humans, a heterozygote mutation has been identified in the AKAP9 gene (substitution of the serine 1570 to leucine); this mutation reduced interaction between the voltage-gated potassium channels (KCNQ1) and AKAP9, reduced cAMP-induced phosphorylation of KCNQ1, and eliminated functional response of the I(Ks) channel to cAMP. This caused prolongation of the action potential and long QT syndrome type 11. Long QT syndromes are heart disorders characterized by a prolonged QT interval on the electrocardiogram. They cause syncope and sudden death in response to exercise or emotional stress. Neurobiological tests have not been carried out in a mouse knock-out of this gene.