Regulation of ubiquitin ligase Nedd4-2 and cardiac sodium and potassium ion channels

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BACKGROUND: Ion channels are membrane proteins which generate electrical signals essential for cell communication. They control many vital physiological processes such as brain function and muscle contractions. The number of channels in the plasma membrane is a key determinant for the amplitude of electrical signals. The channel numbers are tightly regulated by the creation and destruction. Recent work by us and others have shown that a molecule called Nedd4-2 (neural precursor cell expressed, developmentally down-regulated 4-2) mediates the degradation of several ion channels. Presently, it is not known how the activity of Nedd4-2 is regulated. Given its pivotal role, it is therefore critical to understand the regulation of Nedd4-2 function, which further determines the number of ion channels in the cell membrane.