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
| Title: | 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 |
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| Authors: | Henn, Volker; Edemir, Bayram; Stefan, Eduard; Wiesner, Burkhard; Lorenz, Dorothea; Theilig, Franziska; Schmitt, Roland; Vossebein, Lutz; Tamma, Grazia; Beyermann, Michael; Krause, Eberhard; Herberg, Friedrich W.; Valenti, Giovanna; Bachmann, Sebastian; Rosenthal, Walter; Klussmann, Enno |
| Publisher: | Journal of Biological Chemistry |
| Date Published: | June 18, 2004 |
| Reference Number: | 671 |
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.
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This translation by the NDI Foundation is to assist the lay reader. To provide a clear, accessible interpretation of the original article, we eliminated or simplified some technical detail and complicated scientific language. We concentrated our translation on those aspects of the article dealing directly with NDI. The NDI Foundation thanks the researchers for their work toward understanding and more effectively treating this disorder.
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This process contains other steps that are more recently being understood. For example, the joining of PKA to certain subcellular compartments is a prerequisite to the transport of AQP2 from the cell interior to the cell membrane. PKA requires PKA anchoring proteins (AKAPs) in order to bind to these subcellular compartments. However, it is unknown as to which of the family of AKAPs is involved in AQP2’s shuttle to the membrane. Henn, et al., investigated this question using a series of experiments with laboratory rat cell cultures. They identified a new variant of AKAP18, which they dubbed AKAP18d. Their experiments suggest that AKAP18d is involved in the AQP2 shuttle to the cell membrane.
The research team found that, in the kidney, AKAP 18d is found mainly in the collecting duct principal cells, as is AQP2. It is distributed in the cell in the same locations and the same times as AQP2. It is located on the same sacs, called intracellular vesicles, as AQP2 and PKA. Further, AVP initiates AKAP18d movement to the cell membrane. And when cAMP increases in the cell due to AVP, it causes AKAP18d and PKA to separate. The researchers suggest that the anchoring of PKA to AKAP18d is involved in the AQP2 shuttle. The mechanisms by which AKAP18d associates with the vesicles that hold the AQP2 remains to be determined.