The regulation of the urine concentrating mechanism depends on phosphorylation events. In particular, there are transport proteins and channels along the nephron that are each activated or inactivated by phosphorylation at key amino acids. The immediate effect of those phosphorylations is not fully understood, but the outcome of the phosphorylations generally involves trafficking to the membranes where the transporters need to be located in order to fulfill their function. We were the first to prove that phosphorylation of urea transporter UT-A1 resulted in trafficking to the apical membrane surface in order to move urea. Others had shown that aquaporin is similarly phosphorylated resulting in membrane insertion and activation. Recently, we have been investigating the opposing action of dephosphorylation in the regulation of these proteins.
Our lab is interested in the basic effects of dephosphorylation on the membrane association of transport proteins and channels. We also want to understand how dephosphorylation contributes to control of water and urea homeostasis, especially in the situation of the syndrome of inappropriate antidiuretic hormone secretion (SIADH), and vasopressin escape.
As a separate area of interest, we are trying to understand the relationship between responses in the kidney and other organs. To that end, we are exploring fibrosis in kidney and other organs as a consequence of urea transporter involvement and in relation to the renal transport processes. This has resulted in a number of collaborations within the division, in particular with Dr. Xiaonan Wang, looking at the role of microRNAs and their therapeutic potential for chronic kidney disease.
Contact Information
Janet D. Klein, PhD
Associate Professor of Medicine and Physiology Department of Medicine, Renal Division
WMB Rm 3319B
1639 Pierce Drive, NE
Atlanta, GA 30322
Phone: 404-727-9933