AKAP220 colocalizes with AQP2 in the inner medullary collecting ducts.
During dehydration, protein kinase A phosphorylates aquaporin 2 (AQP2) at serine 256 and this is essential for apical membrane sorting of AQP2 in the collecting ducts. A-kinase anchoring proteins (AKAPs) bind protein kinase A and protein phosphatases conferring substrate specificity to these enzymes and localize them to the appropriate intracellular compartment. We found that AKAP220 bound to AQP2 in a yeast two-hybrid screen. Further, it was highly localized to the papilla compared to other regions of the kidney. Using double immunofluorescence and immunoelectron microscopy we found that AKAP220 co-localized with AQP2 in the cytosol of the inner medullary collecting ducts. Forskolin-mediated phosphorylation of AQP2, transiently expressed in COS cells, was increased by AKAP220 co-expression. Our results suggest that AKAP220 may be involved in the phosphorylation of AQP2 by recruiting protein kinase A.
Okutsu
Rie
R
Department of Nephrology, Graduate School of Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
Rai
Tatemitsu
T
Kikuchi
Akira
A
Ohno
Mayuko
M
Uchida
Keiko
K
Sasaki
Sei
S
Uchida
Shinichi
S
D054758:A Kinase Anchor Proteins / Q000378:metabolism*; D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D003600:Cytosol / Q000737:chemistry; D007679:Kidney Medulla / Q000737:chemistry; D007685:Kidney Tubules, Collecting / Q000737:chemistry*; D010766:Phosphorylation; D011485:Protein Binding; D051381:Rats
D054758:A Kinase Anchor Proteins; D051399:Aquaporin 2; D017868:Cyclic AMP-Dependent Protein Kinases