Spatial organisation of AKAP18 and PDE4 isoforms in renal collecting duct principal cells.
A plethora of stimuli including hormones and neurotransmitters mediate a rise of the cellular level of cAMP and thereby activation of protein kinase A (PKA). PKA phosphorylates and thereby modulates the activity of a wide range of cellular targets. It is now appreciated that different stimuli induce the activation of PKA at specific sites where the kinase phosphorylates particular substrates in close proximity. The tethering of PKA to cellular compartments is facilitated by A kinase-anchoring proteins (AKAPs). The incorporation of phosphodiesterases (PDEs) into AKAP-based signalling complexes provides gradients of cAMP that regulate PKA activity locally. An example for a process depending on compartmentalised cAMP/PKA signalling is the arginine-vasopressin (AVP)-mediated water reabsorption in renal collecting duct principal cells. Upon activation through AVP, PKA phosphorylates the water channel aquaporin-2 (AQP-2) located on intracellular vesicles. The phosphorylation triggers the redistribution of AQP2 to the plasma membrane. AKAP-anchored PKA has been shown to be involved in AQP2 shuttling. Here, AKAP18 isoforms and members of the PDE4 family of PDEs are shown to be differentially localised in renal principal cells.
McSorley
Theresa
T
Forschungsinstitut für Molekulare Pharmakologie, Campus Berlin-Buch, Robert-Rössle-Strasse 10, D-13125 Berlin, Germany.
Stefan
Eduard
E
Henn
Volker
V
Wiesner
Burkhard
B
Baillie
George S
GS
Houslay
Miles D
MD
Rosenthal
Walter
W
Klussmann
Enno
E
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism; D001127:Arginine Vasopressin / Q000378:metabolism; D002451:Cell Compartmentation; D000242:Cyclic AMP / Q000378:metabolism; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4; D007527:Isoenzymes / Q000378:metabolism; D007685:Kidney Tubules, Collecting / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D014018:Tissue Distribution
D054758:A Kinase Anchor Proteins; D048868:Adaptor Proteins, Signal Transducing; C487791:Akap7 protein, mouse; D051399:Aquaporin 2; D007527:Isoenzymes; D001127:Arginine Vasopressin; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054703:Cyclic Nucleotide Phosphodiesterases, Type 4