Submitted on December 4, 2007
Accepted on March 31, 2008
Drosophila ortholog of Succinyl-CoA synthetase β subunit: a novel modulator of Drosophila KCNQ channels
Lei Gao1, Hong Fei1, Nathan C. Connors1, Jiaming Zhang1, and Irwin B. Levitan2*
1 Neuroscience, University of Pennsylvania, Philadelphia, Pennsylvania, United States
2 Neuroscience, Univ of Pennsylvania Sch Med, Philadelphia, Pennsylvania, United States
* To whom correspondence should be addressed. E-mail: levitani{at}mail.med.upenn.edu.
Voltage-gated KCNQ potassium channels are responsible for slowly activating potassium currents in heart, brain and other tissues. Functional defects of KCNQ channels are linked with many diseases, including epilepsy and cardiac arrhythmias. Therefore KCNQ potassium channels have been widely studied, especially in the central nervous system. We have identified Drosophila CG11963, which encodes a protein orthologous to the  subunit of mammalian Succinyl-CoA synthetase (SCS, also known as succinate thiokinase), as a novel modulator of Drosophila KCNQ channels. Direct interaction of CG11963 and dKCNQ was demonstrated by yeast two-hybrid and co-immunoprecipitation. Cell surface biotinylation experiments further confirmed that CG11963 resides on the plasma membrane of tsA-201 cells. Co-expression of CG11963 with dKCNQ shifts the conductance-voltage (G-V) relationship of dKCNQ channels to more positive membrane potentials in Chinese hamster ovary (CHO) cells. Moreover, directly dialyzing Glutathione S-transferase (GST) fusion CG11963 protein into CHO cells also shifts the dKCNQ conductance-voltage curve rightward. The effect of CG11963 persists in the presence of 1 mM ATP, a substrate of SCS. Taken together, our data define CG11963 as a new dKCNQ-binding protein capable of modulating the properties of the channel. Our evidence suggests that this modulation is mediated by direct interaction of CG11963 with the channel and is not dependent on ATP.
