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Phosphorylation of rat aquaporin‐4 at Ser 111 is not required for channel gating
Author(s) -
Assentoft Mette,
Kaptan Shreyas,
Fenton Robert A.,
Hua Susan Z.,
Groot Bert L.,
MacAulay Nanna
Publication year - 2013
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22498
Subject(s) - phosphorylation , aquaporin 4 , gating , microbiology and biotechnology , aquaporin , biology , biophysics , protein kinase a , protein phosphorylation , biochemistry
Aquaporin 4 (AQP4) is the predominant water channel in the mammalian brain and is mainly expressed in the perivascular glial endfeet at the brain‐blood interface. AQP4 has been described as an important entry and exit site for water during formation of brain edema and regulation of AQP4 is therefore of therapeutic interest. Phosphorylation of some aquaporins has been proposed to regulate their water permeability via gating of the channel itself. Protein kinase (PK)‐dependent phosphorylation of Ser 111 has been reported to increase the water permeability of AQP4 expressed in an astrocytic cell line. This possibility was, however, questioned based on the crystal structure of the human AQP4. Our study aimed to resolve if Ser 111 was indeed a site involved in phosphorylation‐mediated gating of AQP4. The water permeability of AQP4‐expressing X enopus oocytes was not altered by a range of activators and inhibitors of PKG and PKA. Mutation of Ser 111 to alanine or aspartate (to prevent or mimic phosphorylation) did not change the water permeability of AQP4. PKG activation had no effect on the water permeability of AQP4 in primary cultures of rat astrocytes. Molecular dynamics simulations of a phosphorylation of AQP4.Ser 111 recorded no phosphorylation‐induced change in water permeability. A phospho‐specific antibody, exclusively recognizing AQP4 when phosphorylated on Ser 111 , failed to detect phosphorylation in cell lysate of rat brain stimulated by conditions proposed to induce phosphorylation of this residue. Thus, our data indicate a lack of phosphorylation of Ser 111 and of phosphorylation‐dependent gating of AQP4.

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