Contextual utilization of enzymes in discrete AKAP79/150 signalling complexes.

Cellular function involves the concerted action of signal transduction enzymes. Restriction of enzyme location contributes to the fidelity of each cellular response. A kinase-anchoring proteins (AKAPs) target the cAMP-dependent protein kinase and other signalling enzymes to defined subcellular locations. We have developed a new strategy that combines RNA interference of the endogenous protein and replacement with AKAP79/150 forms unable to anchor selected binding partners. Using this approach we show that AKAP79/150 coordinates different enzyme combinations to modulate the activity of two distinct neuronal ion channels: AMPA-type glutamate receptors and M-type potassium channels. Utilization of distinct enzyme combinations in this manner provides a means to expand the repertoire of cellular events that the same AKAP modulates.