The study of channel modulation by regulatory subunits has attracted considerable attention. Evidence indicates a pivotal role for accessory proteins in the channelosome. For instance, these regulatory subunits are necessary to recapitulate in vivo ion currents and to further understand the physiological role of ion channels. KCNEs are a family of regulatory subunits that interact with a wide range of channels. We have described for the first time a molecular interaction between KCNE4 and the voltage-dependent potassium channel K(V)1.3. The association of KCNE4, which alters the biophysical properties, trafficking and membrane localization of K(V)1.3, functions as an endogenous dominantnegative mechanism. Since both proteins are expressed in the immune system, K(V)1.3/KCNE4 channels may contribute to the fine-tuning of the immune response. Therefore, our results point to KCNE4 as a novel target for immunomodulation. KCNE4 is not the only KCNE which is expressed in leukocytes. All KCNEs (KCNE1-5) are present, and some members demonstrate modulation during proliferation and cancer. In summary, regulatory KCNE subunits are expressed in the immune system. In addition, several voltage-dependent K(+) channels, which could interact with KCNEs, are also detected. Therefore, KCNE subunits may play a yet undiscovered role in the physiology of the immune system.
Keywords: KCNE4; KV1.3; leukocytes; regulatory subunits; voltage-dependent potassium channels.