Electro-neutral KCl co-transporters have been described in a number of different cell types and play important roles in cell volume regulation and in trans-epithelial chloride transport in many nephron segments. The study of KCl co-transporters was limited by a lack of molecular information. Recently the first KCl co-transporter was cloned. Subsequently the principal investigator has cloned two completely new co-transporters KCC3 and KCC4. The long-term goals of this grant proposal are to clarify the molecular mechanisms and physiological role of these KCl co-transporters. Using the newly completed protein sequences the principal investigator has designed a panel of specific antibodies. The goal is to use these antibodies to study the distribution and regulation of the three renal KCCs. Functional studies of these co-transporters will determine which intracellular amino acids determine the volume sensitivity of KCC3 and KCC4 and which transmembrane amino acids determine cation affinity.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK057708-05
Application #
6635260
Study Section
General Medicine B Study Section (GMB)
Program Officer
Ketchum, Christian J
Project Start
2000-05-01
Project End
2004-04-30
Budget Start
2003-05-01
Budget End
2004-04-30
Support Year
5
Fiscal Year
2003
Total Cost
$247,225
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
02115
Mandal, Asim K; Mercado, Adriana; Foster, Andria et al. (2017) Uricosuric targets of tranilast. Pharmacol Res Perspect 5:e00291
Zandi-Nejad, Kambiz; Takakura, Ayumi; Jurewicz, Mollie et al. (2013) The role of HCA2 (GPR109A) in regulating macrophage function. FASEB J 27:4366-74
Acton, Brooke A; Mahadevan, Vivek; Mercado, Adrianna et al. (2012) Hyperpolarizing GABAergic transmission requires the KCC2 C-terminal ISO domain. J Neurosci 32:8746-51
Pan, Dao; Kalfa, Theodosia A; Wang, Daren et al. (2011) K-Cl cotransporter gene expression during human and murine erythroid differentiation. J Biol Chem 286:30492-503
Hartmann, Anna-Maria; Wenz, Meike; Mercado, Adriana et al. (2010) Differences in the large extracellular loop between the K(+)-Cl(-) cotransporters KCC2 and KCC4. J Biol Chem 285:23994-4002
Belenky, M A; Sollars, P J; Mount, D B et al. (2010) Cell-type specific distribution of chloride transporters in the rat suprachiasmatic nucleus. Neuroscience 165:1519-37
Hekmat-Scafe, Daria S; Mercado, Adriana; Fajilan, Adriel A et al. (2010) Seizure sensitivity is ameliorated by targeted expression of K+-Cl- cotransporter function in the mushroom body of the Drosophila brain. Genetics 184:171-83
Mount, David B (2009) Splicing a kinase and the regulation of salt transport. J Am Soc Nephrol 20:1166-8
Mount, David B (2009) The brain in hyponatremia: both culprit and victim. Semin Nephrol 29:196-215
Chang, Min-Hwang; Plata, Consuelo; Sindic, Aleksandra et al. (2009) Slc26a9 is inhibited by the R-region of the cystic fibrosis transmembrane conductance regulator via the STAS domain. J Biol Chem 284:28306-18

Showing the most recent 10 out of 38 publications