Phosphorylation events and the modulation of aquaporin 2 cell surface expression.
OBJECTIVE
This review highlights the role of phosphorylation in the trafficking and targeting of aquaporin 2. Current knowledge will be put into the context of modulating the cell surface expression of aquaporin 2 by vasopressin in renal epithelial cells, which is critical for regulation of urinary concentration and control of fluid and electrolyte homeostasis.


RESULTS
In addition to previously identified phosphorylation sites on aquaporin 2, new data have revealed three other serine residues in the C-terminus whose phosphorylation is altered by vasopressin. Several steps in aquaporin 2 recycling, including exocytosis and endocytosis, are coordinated by phosphorylation and dephosphorylation to regulate cell surface accumulation. Aquaporin 2 phosphorylation on serine 256 regulates aquaporin 2 association with proteins that are involved in trafficking, including hsc/hsp70 and myelin and lymphocyte-associated protein.


CONCLUSIONS
Aquaporin 2 trafficking is regulated by phosphorylation of serine 256 and other amino acid residues in its cytoplasmic domain. These events increase or decrease interaction of aquaporin 2 with key regulatory proteins to determine the cellular distribution and fate of aquaporin 2, both after vasopressin addition and under baseline conditions. Better understanding of these mechanisms may provide new therapeutic avenues for patients with X-linked nephrogenic diabetes insipidus, as well as providing basic cell biological information relevant to membrane trafficking processes in general.
Brown
Dennis
D
MGH-Center for Systems Biology, Program in Membrane Biology and Nephrology Division, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114, USA. Dennis.Brown@mgh.harvard.edu
Hasler
Udo
U
Nunes
Paula
P
Bouley
Richard
R
Lu
Hua A J
HA
D000818:Animals; D051399:Aquaporin 2 / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D004705:Endocytosis; D005089:Exocytosis; D006801:Humans; D010766:Phosphorylation; D021381:Protein Transport; D012694:Serine / Q000378:metabolism; D014667:Vasopressins / Q000494:pharmacology
D051399:Aquaporin 2; D014667:Vasopressins; D012694:Serine