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)

Cyst enlargement in autosomal dominant polycystic kidney disease (ADPKD) results in part from the transport of solute and fluid into the lumen of the cyst. In proximal tubules and thin descending limbs of normal kidneys, the high transepithelial water permeability of these segments is due to the presence of the water channel protein, aquaporin-CHIP (AQP-CHIP, i.e., AQP-1). The collecting ducts of normal kidneys express another member of this gene family, the aquaporin collecting duct (AQP-CD, i.e., AQP-2). The expression and distribution of these two members of the aquaporin gene family were examined in ADPKD and normal human kidneys. In both tissues, Western blotting with the anti-AQP-CHIP antibody revealed a major 28-kDa band. By immunofluorescence, AQP-CHIP was present in proximal tubules and thin descending limbs of Henle of both normal and ADPKD kidneys. In the latter, AQP-CHIP was detected in the epithelia lining 71% of cysts. Many cysts were positive for the proximal tubule marker gp330 (44%). Some cysts expressing AQP-CHIP did not stain for gp330, suggesting a descending thin limb origin, and a few cysts were negative for both markers. In normal human kidney, Western blotting with the anti-AQP-CD antibody revealed a band at 28 kDa. AQP-CD was localized to collecting ducts and did not show colocalization with gp330 in normal human kidney. In ADPKD kidney, AQP-CD was expressed by only 8% of cysts. In summary, water channels, primarily AQP-CHIP, are expressed in epithelial cells lining cysts in approximately 80% of cysts in ADPKD kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Water channel expression in human ADPKD kidneys. 753

Two water channel homologs were cloned recently from rat kidney, mercurial-insensitive water channel (MIWC) and glycerol intrinsic protein (GLIP). Polyclonal antibodies were raised against synthetic C-terminal peptides and purified by affinity chromatography. MIWC and GLIP antibodies recognized proteins in rat kidney with an apparent molecular mass of 30 and 27 kDa, respectively, and did not cross-react. By immunofluorescence, MIWC and GLIP were expressed together on the basolateral plasma membrane of collecting duct principal cells in kidney. By immunohistochemistry, MIWC and GLIP were expressed on tracheal epithelial cells with greater expression of GLIP on the basal plasma membrane and MIWC on the lateral membrane; only MIWC was expressed in bronchial epithelia. In eye, GLIP was expressed in conjunctival epithelium, whereas MIWC was found in iris, ciliary body, and neural cell layers in retina. MIWC and GLIP colocalized on the basolateral membrane of villus epithelial cells in colon and brain ependymal cells. Expression of MIWC and GLIP was not detected in small intestine, liver, spleen, endothelia, and cells that express water channels CHIP28 or WCH-CD. These studies suggest water/solute transporting roles for MIWC and GLIP in the urinary concentrating mechanism, cerebrospinal fluid absorption, ocular fluid balance, fecal dehydration, and airway humidification. The unexpected membrane colocalization of MIWC and GLIP in several tissues suggests an interaction at the molecular and/or functional levels.
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PMID:Immunolocalization of the mercurial-insensitive water channel and glycerol intrinsic protein in epithelial cell plasma membranes. 753 65

Aquaporin 2 is a collecting duct water channel that is located in apical vesicles and in the apical plasma membrane of collecting duct principal cells. It shares 42% identity with the proximal tubule/thin descending limb water channel, CHIP28. The present study was aimed at addressing three questions concerning the location and behavior of the AQP2 protein under different conditions. First, does the AQP2 channel relocate to the apical membrane after vasopressin treatment? Our results show that AQP2 is diffusely distributed in cytoplasmic vesicles in collecting duct principal cells of homozygous Brattleboro rats that lack vasopressin. In rats injected with exogenous vasopressin, however, AQP2 became concentrated in the apical plasma membrane of principal cells, as determined by immunofluorescence and immunogold electron microscopy. This behavior is consistent with the idea that AQP2 is the vasopressin-sensitive water channel. Second, is the cellular location of AQP2 modified by microtubule disruption? In normal rats, AQP2 has a mainly apical and subapical location in principal cells, but in colchicine-treated rats, it is distributed on vesicles that are scattered throughout the entire cytoplasm. This is consistent with the dependence on microtubules of apical protein targeting in many cell types, and explains the inhibitory effect of microtubule disruption on the hydroosmotic response to vasopressin in sensitive epithelia, including the collecting duct. Third, is AQP2 present in neonatal rat kidneys? We show that AQP2 is abundant in principal cells from neonatal rats at all days after birth. The detection of AQP2 in early neonatal kidneys indicates that a lack of this protein is not responsible for the relatively weak urinary concentrating response to vasopressin seen in neonatal rats.
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PMID:The AQP2 water channel: effect of vasopressin treatment, microtubule disruption, and distribution in neonatal rats. 753 96

MIWC is a 32 kDa mercurial-insensitive water channel [Hasegawa et al. (1994) J. Biol. Chem. 269, 5497-5500] expressed in kidney collecting duct, brain ependymal cells, airways, and other tissues. We showed recently that the homologous water channel CHIP28 spanned the endoplasmic reticulum (ER) membrane 4 times with N- and C-termini in the cytoplasm [Skach et al., (1994) J. Cell Biol. 125, 803-815]. Hydropathy analysis of MIWC indicated up to eight hydrophobic regions (HRs) comprising potential membrane-spanning domains. To determine MIWC transmembrane topology at the ER, 10 cDNA chimeras were constructed which encoded increasing lengths of MIWC upstream from a reporter epitope (prolactin P-domain) at residues 13, 46, 73, 92, 120, 140, 164, 209, 276, and 2097, corresponding to putative polar extramembrane loops in the MIWC sequence. The chimeras were translated cell-free (rabbit reticulocyte lysate+ER-derived microsomes) and in Xenopus oocytes. Peptide chains were labeled with [35S]methionine and immunoprecipitated with a P-domain antibody. Transmembrane topology as determined by protease accessibility of the P-reporter indicated six membrane-spanning domains with N- and C-termini in the cytoplasm. The predicted topology was confirmed by demonstrating N-linked glycosylation at native residue N131 and an engineered consensus site at residue 197. Membrane integration of the nascent chain, as assayed by extractability at pH 11.5, occurred after synthesis of the first HR (residues 1-46). Translocation was terminated by a stop transfer sequence in the second HR (residues 32-73) as demonstrated by translation of the heterologous construct, [prolactin signal sequence]-[globin]-[HR2]-P.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Distinct biogenesis mechanisms for the water channels MIWC and CHIP28 at the endoplasmic reticulum. 754 Dec 39

The sites of water transport along the nephron are well characterized, but the molecular basis of renal water transport remains poorly understood. CHIP28 is a 28-kD integral protein which was proposed to mediate transmembrane water movement in red cells and kidney (Preston, G. M., T. P. Carroll, W. B. Guggino, and P. Agre. 1992. Science [Wash. DC]. 256:385-387). To determine whether CHIP28 could account for renal epithelial water transport, we used specific polyclonal antibodies to quantitate and localize CHIP28 at cellular and subcellular levels in rat kidney using light and electron microscopy. CHIP28 comprised 3.8% of isolated proximal tubule brush border protein. Except for the first few cells of the S1 segment, CHIP28 was immunolocalized throughout the convoluted and straight proximal tubules where it was observed in the microvilli of the apical brush border and in basolateral membranes. Very little CHIP28 was detected in endocytic vesicles or other intracellular structures in proximal tubules. Uninterrupted, heavy immunostaining of CHIP28 was also observed over both apical and basolateral membranes of descending thin limbs, including both short and long loops of Henle. These nephron sites have constitutively high osmotic water permeabilities. CHIP28 was not detected in ascending thin limbs, thick ascending limbs, or distal tubules, which are highly impermeable to water. Moreover, CHIP28 was not detected in collecting duct epithelia, where water permeability is regulated by antidiuretic hormone. These determinations of abundance and structural organization provide evidence that the CHIP28 water channel is the predominant pathway for constitutive transepithelial water transport in the proximal tubule and descending limb of Henle's loop.
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PMID:CHIP28 water channels are localized in constitutively water-permeable segments of the nephron. 767 19

The tissue distribution of mRNA encoding rat kidney water channel CHIP28k was determined by in situ hybridization. cDNA encoding rat kidney CHIP28k was isolated by homology to human erythrocyte CHIP28 (G. M. Preston and P. Agre. Proc. Natl. Acad. Sci. USA 88: 11110-11114, 1991) and used to construct 155-base 35S-labeled cRNA sense and antisense probes corresponding to base pair 7-162. Fixed and frozen tissues were cut in 6- to 12- microns sections, hybridized with probes at 55 degrees C for 16 h, and exposed for 5-9 days. In renal cortex, CHIP28k mRNA was detected intensely on proximal tubule epithelial cells but not in glomeruli or collecting duct. Hybridization to proximal tubule was strongest in deep renal cortex. In no study was there significant hybridization of sense cRNA probe. In renal papilla, CHIP28k mRNA was detected in only a fraction of tubules corresponding to thin limbs of Henle. Hybridization in spleen was observed in red splenic pulp containing erythroid precursors but not in white pulp. In colon, there was selective hybridization in crypt epithelial cells but not in villus epithelial cells or nonepithelial structures. In lung, hybridization was observed in alveolar epithelial cells. In eye, there was selective hybridization in corneal endothelium and ciliary body. No hybridization was observed in any cell types in liver. Northern analysis revealed a 2.8-kilobase mRNA encoding CHIP28k in kidney cortex and papilla but not in brain, skeletal muscle, and liver. These results indicate a wide and highly selective tissue distribution of mRNA encoding the CHIP28k water channel.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Tissue-specific expression of mRNA encoding rat kidney water channel CHIP28k by in situ hybridization. 767 51

In searching for a basolateral membrane water transporter in rat kidney with homology to channel forming integral protein (CHIP28), water channel-collecting duct (WCH-CD), and mercurial-insensitive water channel (MIWC), we cloned a new member of the major intrinsic protein family (GLIP, GLycerol Intrinsic Protein). GLIP cDNA had an 855-base pair open reading frame encoding a 30.5-kDa protein with 19-23% amino acid identity to the water channels and 36% identity to the bacterial glycerol facilitator GlpF. Northern blot analysis showed a 5.5-kilobase mRNA encoding GLIP in kidney, brain, and lung; RT-PCR/Southern blot analysis indicated expression of GLIP in kidney, brain, lung, eye, colon, stomach, and skeletal muscle, but not in heart, liver, and spleen. In situ hybridization in rat kidney showed GLIP mRNA expression in medullary collecting duct. Immunofluorescence with a peptide-derived polyclonal antibody showed GLIP protein expression in basolateral membrane of kidney collecting duct principal cells and brain meningeal cells. Functional measurements in Xenopus oocytes expressing GLIP cRNA showed a > 20-fold increase in [3H]glycerol uptake compared with water-injected oocytes; glycerol uptake was inhibited 88% by diisothiocyanodisulfonic stilbene (0.2 mM) and 36% by phloretin (0.25 mM). GLIP did not function as a transporter for water, urea, inositol, glucose, lactate, and monovalent ions. Glycerol uptake in oocytes expressing CHIP28 and MIWC was not different from that in water-injected controls. GLIP represents the first mammalian water channel homolog that selectively transports a solute other than water. The physiological substrate(s) and role(s) of GLIP remain to be elucidated.
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PMID:Cloning of a water channel homolog expressed in brain meningeal cells and kidney collecting duct that functions as a stilbene-sensitive glycerol transporter. 806 28

Antidiuretic hormone (ADH) stimulation of renal epithelial cells elicits a large increase in apical membrane osmotic water permeability (Pf) produced by the fusion of water channel containing vesicles with the apical membrane. Removal of ADH stimulation results in retrieval of apical water channels into a specialized non-acidic endosomal compartment. Previous studies (Sabolic, I., Wuarin, F., and Shi, L. B. (1992) J. Cell Biol. 119, 111-122) have shown that water channel containing papillary endosomes labeled with fluorescein-dextran can be isolated from rat renal papilla. We have utilized small particle flow sorting methodology to both monitor and improve upon the purification of these water channel containing endosomes (WCV). Flow cytometry analysis on a vesicle-by-vesicle basis demonstrates that WCV are homogeneous with respect to entrapped fluorescein-dextran, the apical membrane enzyme marker leucine amino peptidase and ultrastructural morphology. WCV do not acidify their luminal contents after addition of Mg-ATP but contain abundant functional water channels (Pf0.28 cm/s at 23 degrees C) as determined by stopped flow fluorimetry. SDS-polyacrylamide gel electrophoresis analysis shows that purified WCV are composed of 20 major protein bands. To determine the identity of WCV water channels, WCV proteins were probed with affinity purified antisera recognizing two renal water channel proteins. These include Aquaporin-CHIP found in the proximal tubule and thin descending limb of Henle and the candidate ADH water channel protein WCH-1 or Aquaporin- (AQP) CD present in the ADH-responsive epithelial cells of the collecting duct. These data reveal that WCV contained little or no AQP-CHIP protein. In contrast, WCV are highly enriched for AQP-CD protein. Together, these data define the protein composition of the papillary WCV and link directly the presence of functional apical membrane water channels with the presence of the AQP-CD protein.
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PMID:Characterization of purified endosomes containing the antidiuretic hormone-sensitive water channel from rat renal papilla. 816 2

The localization and transporting properties of a kidney protein homologous to human erythrocyte protein CHIP28 was evaluated. The cDNA encoding rat kidney protein CHIP28k was isolated from a rat renal cortex cDNA library. A 2.8-kb cDNA was identified which contained an 807 bp open reading frame encoding a 28.8 kD protein with 94% amino acid identity to CHIP28. in vitro translation of CHIP28k cDNA in rabbit reticulocyte lysate generated a 28-kD protein; addition of ER-derived microsomes gave a 32-kD transmembrane glycoprotein. Translation of truncated RNA demonstrated glycosylation of residue Asn42 which is predicted to lie between the first and second transmembrane domains. Expression of in vitro transcribed mRNA encoding CHIP28k in Xenopus oocytes increased oocyte osmotic water permeability (Pf) from (4 +/- 1) x 10(-4) to (33 +/- 4) x 10(-4) cm/s at 10 degrees C; the increase in oocyte Pf was weakly temperature dependent and inhibited by HgCl2. Two-electrode voltage clamp measurements indicated that CHIP28k was not permeable to ions. Oocyte Pf also increased with expression of total mRNA from kidney cortex and papilla; the increase in Pf with mRNA from cortex, but not kidney papilla, was blocked by coinjection with excess antisense CHIP28k cRNA. In situ hybridization of a 150 base cRNA antisense probe to tissue sections from rat kidney showed selective CHIP28k localization to epithelial cells in proximal tubule and thin descending limb of Henle. Pf in purified apical membrane vesicles from rat and human proximal tubule, and in proteoliposomes reconstituted with purified protein, was very high and inhibited by HgCl2; stripping of apical vesicles with N-lauroylsarcosine enriched a 28-kD protein by 25-fold and yielded a vesicle population with high water, but low urea and proton permeabilities. CHIP28k identity was confirmed by NH2-terminus sequence analysis. These results indicate that CHIP28k is a major and highly selective water transporting protein in the kidney proximal tubule and thin descending limb of Henle, but not collecting duct.
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PMID:Cloning, functional analysis and cell localization of a kidney proximal tubule water transporter homologous to CHIP28. 842 Oct 53

There is now firm evidence that water transporting proteins are expressed in renal and extrarenal tissues. In the kidney, proximal-type (CHIP28) and collecting duct (WCH-CD) water channels have been identified. We have cloned three kidney cDNAs with homology to the water channel (aquaporin) family, including a mercurial-insensitive water channel (MIWC), and a glycerol-transporting protein (GLIP) in collecting duct basolateral membrane. To elucidate water transporting mechanisms, a series of molecular and spectroscopic studies were carried out on purified CHIP28 protein and expressed chimeric and mutated CHIP28 cDNAs. The results indicate that CHIP28 transports water selectively, that CHIP28 monomers are assembled in membranes as tetramers, but that individual monomers function independently. Monomers contain multiple membrane-spanning helical domains. Based on these data and recent electron crystallography results, a model for water transport is proposed in which water moves through narrow pores located within individual CHIP28 monomers.
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PMID:Structure and function of kidney water channels. 856 68


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