Distinct enzyme combinations in AKAP signalling complexes permit functional diversity

Hoshi N, Langeberg LK and Scott JD
Source: Nat Cell Biol
Publication Date: (2005)
Issue: 7(11): 1066-1073
Research Area:
Cells used in publication:
Neuron, hippo/cortical, rat
Species: rat
Tissue Origin: brain
Neuron, mesencephalic, rat
Species: rat
Tissue Origin: brain
Neuron, hippocampal, rat
Species: rat
Tissue Origin: brain
Nucleofector® I/II/2b
Specificity in cell signalling can be influenced by the targeting of different enzyme combinations to substrates. The A-kinase anchoring protein AKAP79/150 is a multivalent scaffolding protein that coordinates the subcellular localization of second-messenger-regulated enzymes, such as protein kinase A, protein kinase C and protein phosphatase 2B. We developed a new strategy that combines RNA interference of the endogenous protein with a protocol that selects cells that have been rescued with AKAP79/150 forms that are unable to anchor selected enzymes. 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.