Distinct enzyme combinations in AKAP signalling complexes permit functional diversity.
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.
Hoshi
Naoto
N
Howard Hughes Medical Institute, Vollum Institute, Oregon Health and Science University, 3181 S.W. Sam Jackson Park Road, Portland, OR 97239, USA.
Langeberg
Lorene K
LK
Scott
John D
JD
D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism / Q000502:physiology*; D019703:Calcineurin / Q000378:metabolism* / Q000502:physiology; D065095:Calcineurin Inhibitors; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D000074288:Discs Large Homolog 1 Protein; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism / Q000502:physiology*; D008954:Models, Biological; D018721:Muscarinic Agonists; D015221:Potassium Channels / Q000378:metabolism; D034622:RNA Interference; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; D065095:Calcineurin Inhibitors; D002352:Carrier Proteins; C513314:DLG1 protein, human; D000074288:Discs Large Homolog 1 Protein; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D018721:Muscarinic Agonists; D015221:Potassium Channels; D018350:alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D019703:Calcineurin