Our research project focuses on the study of unresolved problems of the mechanisms of ion transport across the apical and basolateral membranes of defined tubule segments. We shall apply tubule perfusion and patch- clamp techniques to evaluate cellular and molecular transport mechanisms of Na,K,C1 and H and their physiological regulation. First, we propose to explore the mechanism of proximal tubule chloride transport with emphasis o apical formate-chloride and oxalate-chloride exchange. These studies will be directed at the nature of the recycling mechanisms of formate and oxalate and the participation of the anion exchangers in the physiological regulation of proximal tubule NaCI transport. We shall also investigate the role of chloride channels in the basolateral membrane in mediating net chloride reabsorption. Second, we propose to study the interaction of Na,K,Ca and H transport in principal tubule cells. We shall analyse their acid-base transport mechanisms, and explore their regulation and interaction with net sodium and potassium transport. Our studies will provide insights into """"""""membrane cross-talk"""""""" and the signaling pathways affecting Na,K,pH and Ca homeostasis. Third, we propose to explore the apical low-conductance K channel in principal tubule cells. We shall address unresolved problems of conduction mechanism and physiological regulation. We also plan to explore a recently clone ATP-sensitive channel and compare its properties with native K channels in principal tubule cells.

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Kim, Jun-Mo; Xu, Shuhua; Guo, Xiaoyun et al. (2018) Urinary bladder hypertrophy characteristic of male ROMK Bartter's mice does not occur in female mice. Am J Physiol Regul Integr Comp Physiol 314:R334-R341
Gassaway, Brandon M; Petersen, Max C; Surovtseva, Yulia V et al. (2018) PKC? contributes to lipid-induced insulin resistance through cross talk with p70S6K and through previously unknown regulators of insulin signaling. Proc Natl Acad Sci U S A 115:E8996-E9005
Gilder, Allison L; Chapin, Hannah C; Padovano, Valeria et al. (2018) Newly synthesized polycystin-1 takes different trafficking pathways to the apical and ciliary membranes. Traffic 19:933-945
Barber, Karl W; Muir, Paul; Szeligowski, Richard V et al. (2018) Encoding human serine phosphopeptides in bacteria for proteome-wide identification of phosphorylation-dependent interactions. Nat Biotechnol 36:638-644
Scholl, Ute I; Stölting, Gabriel; Schewe, Julia et al. (2018) CLCN2 chloride channel mutations in familial hyperaldosteronism type II. Nat Genet 50:349-354
Barber, Karl W; Rinehart, Jesse (2018) The ABCs of PTMs. Nat Chem Biol 14:188-192
Barber, Karl W; Miller, Chad J; Jun, Jay W et al. (2018) Kinase Substrate Profiling Using a Proteome-wide Serine-Oriented Human Peptide Library. Biochemistry 57:4717-4725
Castañeda-Bueno, Maria; Arroyo, Juan Pablo; Zhang, Junhui et al. (2017) Phosphorylation by PKC and PKA regulate the kinase activity and downstream signaling of WNK4. Proc Natl Acad Sci U S A 114:E879-E886
Mohler, Kyle; Aerni, Hans-Rudolf; Gassaway, Brandon et al. (2017) MS-READ: Quantitative measurement of amino acid incorporation. Biochim Biophys Acta Gen Subj 1861:3081-3088
D'Lima, Nadia G; Khitun, Alexandra; Rosenbloom, Aaron D et al. (2017) Comparative Proteomics Enables Identification of Nonannotated Cold Shock Proteins in E. coli. J Proteome Res 16:3722-3731

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