Identification of a novel A-kinase anchoring protein 18 isoform and evidence for its role in the vasopressin-induced aquaporin-2 shuttle in renal principal cells

J Biol Chem. 2004 Jun 18;279(25):26654-65. doi: 10.1074/jbc.M312835200. Epub 2004 Mar 22.


Arginine vasopressin (AVP) increases the water permeability of renal collecting duct principal cells by inducing the fusion of vesicles containing the water channel aquaporin-2 (AQP2) with the plasma membrane (AQP2 shuttle). This event is initiated by activation of vasopressin V2 receptors, followed by an elevation of cAMP and the activation of protein kinase A (PKA). The tethering of PKA to subcellular compartments by protein kinase A anchoring proteins (AKAPs) is a prerequisite for the AQP2 shuttle. During the search for AKAP(s) involved in the shuttle, a new splice variant of AKAP18, AKAP18delta, was identified. AKAP18delta functions as an AKAP in vitro and in vivo. In the kidney, it is mainly expressed in principal cells of the inner medullary collecting duct, closely resembling the distribution of AQP2. It is present in both the soluble and particulate fractions derived from renal inner medullary tissue. Within the particulate fraction, AKAP18delta was identified on the same intracellular vesicles as AQP2 and PKA. AVP not only recruited AQP2, but also AKAP18delta to the plasma membrane. The elevation of cAMP caused the dissociation of AKAP18delta and PKA. The data suggest that AKAP18delta is involved in the AQP2 shuttle.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • A Kinase Anchor Proteins
  • Adaptor Proteins, Signal Transducing*
  • Animals
  • Aquaporin 2
  • Aquaporins / chemistry*
  • Arginine Vasopressin / chemistry
  • Blotting, Northern
  • Blotting, Western
  • Carrier Proteins / chemistry*
  • Carrier Proteins / physiology*
  • Cell Line
  • Cell Membrane / metabolism
  • Cells, Cultured
  • Cloning, Molecular
  • Cyclic AMP / metabolism
  • DNA, Complementary / metabolism
  • Enzyme Activation
  • Fluorescence Resonance Energy Transfer
  • Gene Library
  • Glutathione Transferase / metabolism
  • Humans
  • Immunohistochemistry
  • Kidney / cytology*
  • Kidney / metabolism
  • Kidney Medulla / metabolism
  • Kinetics
  • Membrane Proteins / chemistry*
  • Membrane Proteins / physiology*
  • Precipitin Tests
  • Protein Binding
  • Protein Conformation
  • Protein Isoforms
  • Protein Transport
  • RNA / chemistry
  • RNA, Messenger / metabolism
  • Rats
  • Recombinant Fusion Proteins / metabolism
  • Subcellular Fractions
  • Surface Plasmon Resonance
  • Time Factors
  • Vasopressins / chemistry*


  • A Kinase Anchor Proteins
  • AKAP7 protein, human
  • AQP2 protein, human
  • Adaptor Proteins, Signal Transducing
  • Aqp2 protein, rat
  • Aquaporin 2
  • Aquaporins
  • Carrier Proteins
  • DNA, Complementary
  • Membrane Proteins
  • Protein Isoforms
  • RNA, Messenger
  • Recombinant Fusion Proteins
  • Vasopressins
  • Arginine Vasopressin
  • RNA
  • Cyclic AMP
  • Glutathione Transferase