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Molecular mechanisms of ion transport in the kidney.
Our general goal is to characterize the molecular mechanisms underlying regulation of sodium, acid-base, and anion excretion by the kidney. Toward this end, our work is primarily focused on membrane transport proteins mediating ion exchange, namely NHE isoforms mediating Na +-H + exchange, and SLC26 isoforms mediating anion exchange. One approach involves the generation of isoform-specific polyclonal and monoclonal antibodies to identify the cellular and subcellular sites of expression of ion exchangers in the kidney and other tissues, and to study their biosynthesis and assembly into multimeric complexes. A complementary approach is to use mice with targeted gene disruption to elucidate the physiological roles of ion exchangers and associated proteins under in vivo conditions. For example, recent work with mice lacking anion exchanger Slc26a6, which can function as an oxalate transporter, revealed a phenotype of kidney stones as shown in the figure.
Figure
caption: Urolithiasis in mice lacking anion exchanger Slc26a6. Illustrated are the bladder of a wild-type mouse with no stones, and the bladder from an Slc26a6 null mouse that was filled with calcium oxalate stones. Jiang, Nature Genetics, 2006.
Recent publications:
Girardi, A.C.C., Knauf, F., Demuth, H.-U., Aronson, P.S. Role of dipeptidyl peptidase IV in regulating activity of Na +-H + exchanger isoform NHE3. Am. J. Physiol. 287:C1238-C1245, 2004.
Goyal, S., Mentone, S., and Aronson, P.S. Immunolocalization of NHE8 in rat kidney. Am. J. Physiol. 288:F530-F538, 2005. Wang, Z., Wang, T., Petrovic, S., Tuo, B., Riederer, B., Barone, S., Lorenz, J., Seidler, U., Aronson, P.S., and Soleimani, M. Kidney and intestine transport defects in Slc26a6 null mice. Am. J. Physiol. 288:C957-C965, 2005.
Kocinsky, H., Girardi, A.C., Biemesderfer, D., Nguyen, T., Mentone, S., Orlowski, J., and Aronson, P.S. Use of phosphospecific antibodies to determine the phosphorylation of endogenous Na +-H + Exchanger NHE3 at PKA consensus sites. Am. J. Physiol. 289: F249-F258, 2005.
Thomson, R.B., Wang, T., Thomson, B.R., Tarrats, L., Girardi, A., Mentone, S., Soleimani, M., Kocher, O., and Aronson, P.S. Role of PDZK1 in membrane expression of renal brush border ion exchangers. Proc. Natl. Acad. Sci. USA 102:13331-13336, 2005.
Dudas, P.L., Mentone, S., Greineder, C.F., Biemesderfer, D., and Aronson, P.S. Immunolocalization of anion transporter Slc26a7 in mouse kidney. Am. J. Physiol., in press.
Jiang, Z., Asplin, J.R., Evan, A.P., Rajendran, V.M., Velazquez, H., Nottoli, T.P., Binder, H.J., and Aronson, P.S. Calcium oxalate urolithiasis in mice lacking anion transporter Slc26a6. Nature Genetics, in press.
peter.aronson@yale.edu
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