This application seeks continued support for a broad program of research directed towards elucidation of the mechanisms that control and regulate electrolyte transport across cell membranes. Investigators will use a wide variety of approaches and techniques to evaluate (1) molecular mechanisms determining passive and active translocation across individual cell membranes and across epithelia, (2) the relationship between transport and cell metabolism and (3) electrical manifestation of ion transport. In addition to physiological transport studies, pathological transport defects and the site and mechanism of action of drugs and of hormones will also be investigated. Transport will be studied on isolated enzyme systems in vitro (ATPase), in single cells (red blood cells, neurospora), isolated epithelia (renal tubule, intestinal mucosa, amphibian and mammalian bladder) and on organ systems (kidney, liver and intestine). Vesicular preparations of epithelia and transport in cell cultures will also be evaluated. A wide spectrum of approaches will be used. These will include measurements of transport rates, tracer fluxes, fluorescence, cell pH, cell ion activities and electron probe analysis of elements. In addition, electrophysiological and immunocytological techniques will be employed. Finally, we shall continue the use of electron-microscopic methods to investigate the correlation between cell membrane structure and electrolyte and fluid transport.

Project Start
1979-03-01
Project End
1989-02-28
Budget Start
1985-12-01
Budget End
1986-11-30
Support Year
13
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Yale University
Department
Type
Schools of Medicine
DUNS #
082359691
City
New Haven
State
CT
Country
United States
Zip Code
06520
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
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
Li, Jing; Hatano, Ryo; Xu, Shuhua et al. (2017) Gender difference in kidney electrolyte transport. I. Role of AT1a receptor in thiazide-sensitive Na+-Cl- cotransporter activity and expression in male and female mice. Am J Physiol Renal Physiol 313:F505-F513
Inoue, Kazunori; Balkin, Daniel M; Liu, Lijuan et al. (2017) Kidney Tubular Ablation of Ocrl/Inpp5b Phenocopies Lowe Syndrome Tubulopathy. J Am Soc Nephrol 28:1399-1407
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

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