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MEMBRANE TRANSPORTERS, ION CHANNELS, AND PUMPS

RACK1 is a BK_Ca channel binding protein

¹Molecular Cardiology Research Institute, Tufts-New England Medical Center, and ²The Department of Neuroscience, Tufts University School of Medicine, Boston, Massachusetts

Submitted 12 June 2006 ; accepted in final form 6 December 2006

The large conductance calcium-activated potassium channel, or BK_Ca channel, plays an important feedback role in a variety of physiological processes, including neurotransmitter release and smooth muscle contraction. Some reports have suggested that this channel forms a stable complex with regulators of its function, including several kinases and phosphatases. To further define such signaling complexes, we used the yeast two-hybrid system to screen a human aorta cDNA library for proteins that bind to the BK_Ca channel's intracellular, COOH-terminal "tail". One of the interactors we identified is the protein receptor for activated C kinase 1 (RACK1). RACK1 is a member of the WD40 protein family, which also includes the G protein -subunits. Consistent with an important role in BK_Ca-channel regulation, RACK1 has been shown to be a scaffolding protein that interacts with a wide variety of signaling molecules, including cSRC and PKC. We have confirmed the interaction between RACK1 and the BK_Ca channel biochemically with GST pull-down and coimmunoprecipitation experiments. We have observed some co-localization of RACK1 with the BK_Ca channel in vascular smooth muscle cells with immunocytochemical experiments, and we have found that RACK1 has effects on the BK_Ca channel's biophysical properties. Thus RACK1 binds to the BK_Ca channel and it may form part of a BK_Ca-channel regulatory complex in vascular smooth muscle.

calcium-activated potassium channel; protein kinase C; smooth muscle