Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Channel inducing factor (CHIF) is a novel cDNA recently cloned from a rat distal colon cDNA library of dexamethasone-treated animals. While its expression in Xenopus oocytes evokes a potassium channel activity similar to that induced by Isk (minK), its cellular role is not clear. CHIF exhibits significant homologies with proteins that are putatively regulatory (phospholemman, gamma-subunit of Na(+)-K(+)-ATPase, Mat-8) while it differs from the small-conductance potassium channel Isk. We have studied the tissue specificity of CHIF expression in rat by in situ hybridization. CHIF is selectively present in the distal parts of the nephron (medullary and papillary collecting ducts and end portions of cortical collecting tubule) and in the epithelial cells of the distal colon. No expression of CHIF was found in renal proximal tubule, loop of Henle and distal tubule, proximal colon, small intestine, lung, choroid plexus, salivary glands, or brain. To gain some insight into CHIF function, we have investigated, using in situ hybridization and ribonuclease protection assay, whether CHIF mRNA expression could be altered in some situations. In the distal colon, corticosteroid hormones, sodium restriction, low-potassium diet, and metabolic acidosis significantly increased CHIF mRNA expression. In the kidney, metabolic acidosis was the only condition that showed an increase in CHIF mRNA expression. Some of these treatments also altered the expression of the colonic H(+)-K(+)-ATPase mRNA. In summary, CHIF mRNA is selectively expressed in the medullary collecting duct of the kidney and in the epithelium of the distal colon; its expression varies differently in these two target tissues after alterations in corticosteroid status, potassium depletion, and metabolic acidosis. The precise cell-specific functions of CHIF remain to be established.
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PMID:Cellular localization and regulation of CHIF in kidney and colon. 884 4

The gamma subunit of Na/K/ATPase is a small membrane protein that shares homologies with other members of the FXYD family, like phospholemman and CHIF (corticosteroid hormone-induced factor). Both the gamma subunit and CHIF modulate sodium pump properties. The gamma subunit increases the apparent affinity of the pump for ATP and reduces its apparent affinity for sodium. CHIF, in contrast, augments its apparent affinity for sodium. Gamma subunit expression is essentially restricted to the kidney, with two main splice variants, gammaa and gammab, which differ only at their extracellular N-termini. We have investigated in detail the cell-specific expression of the two splice variants of gamma within the kidney and compared it to that of CHIF. While both gamma variants affect catalytic properties of the pump (without detectable difference between a and b forms), their localization along the nephron is partially distinct. Both variants are coexpressed in the proximal tubule and in the medullary part of the thick ascending limb of Henle's loop (TAL). In contrast, their expression differs in the downstream tubular segments. Within the renal cortex, the sole gamma a variant was found in macula densa cells and in principal cells of the initial parts of the collecting duct. Gamma b is in the cortical part of the TAL. Outer and inner medullary collecting ducts lack detectable gamma expression. These latter nephron segments express CHIF, and no overlap between gamma and CHIF expression along the nephron was observed. Such distinct cell-specific expression argues for complementary roles to modulate Na/K/ATPase activity.
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PMID:Cell-specific expression of three members of the FXYD family along the renal tubule. 1276 61

The final adjustment of urine volume occurs in the inner medullary collecting duct (IMCD), chiefly mediated by the water channel aquaporin 2 (AQP2). With vasopressin stimulation, AQP2 accumulation in the apical plasma membrane of principal cells allows water reabsorption from the lumen. We report that FXYD1 (phospholemman), better known as a regulator of Na,K-ATPase, has a role in AQP2 trafficking. Daytime urine of Fxyd1 knockout mice was more dilute than WT despite similar serum vasopressin, but both genotypes could concentrate urine during water deprivation. FXYD1 was found in IMCD. In WT mice, phosphorylated FXYD1 was detected intracellularly, and vasopressin induced its dephosphorylation. We tested the hypothesis that the dilute urine in knockouts was caused by alteration of AQP2 trafficking. In WT mice at baseline, FXYD1 and AQP2 were not strongly co-localized, but elevation of vasopressin produced translocation of both FXYD1 and AQP2 to the apical plasma membrane. In kidney slices, baseline AQP2 distribution was more scattered in the Fxyd1 knockout than in WT. Apical recruitment of AQP2 occurred in vasopressin-treated Fxyd1 knockout slices, but upon vasopressin washout, there was more rapid reversal of apical AQP2 localization and more heterogeneous cytoplasmic distribution of AQP2. Notably, in sucrose gradients, AQP2 was present in a detergent-resistant membrane domain that had lower sedimentation density in the knockout than in WT, and vasopressin treatment normalized its density. We propose that FXYD1 plays a role in regulating AQP2 retention in apical membrane, and that this involves transfers between raft-like membrane domains in endosomes and plasma membranes.
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PMID:Impaired AQP2 trafficking in Fxyd1 knockout mice: A role for FXYD1 in regulated vesicular transport. 2915 57