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)

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

It was shown recently that water channel homologs MIWC (mercurial insensitive water channel) and GLIP (glycerol intrinsic protein) colocalized in basolateral membranes of kidney collecting duct, tracheal and colonic epithelia, and in brain pia mater. We report here an extensive immunolocalization study of MIWC and GLIP in non-epithelial and glandular epithelial tissues in rat. Immunogold electron microscopy confirmed colocalization of MIWC and GLIP in basolateral membrane of principal cells in kidney collecting duct. However, in other epithelia, MIWC but not GLIP was expressed in basolateral membrane of parietal cells in stomach, and in excretory tubules of salivary and lacrimal glands; GLIP but not MIWC was expressed in transitional epithelium of urinary bladder and skin epidermis. In the central nervous system, MIWC was strongly expressed in the ependymal layer lining the aqueductal system, and in astrocytes throughout the spinal cord and in selected regions of brain. MIWC was also expressed in a plasma membrane pattern in skeletal, but not smooth or cardiac muscle. Neither protein was expressed in small intestine, testis, liver, spleen and nerve. The tissue-specific expression of MIWC suggests a role in fluid transport and/or cell volume regulation in stomach and glandular epithelia. The functional role of MIWC expression in the neuromuscular system and of GLIP expression in skin and urinary bladder is uncertain. The specific cellular sites of MIWC expression (astrocytes, trachea, sarcolemma, gastric parietal cells and kidney principal cells) correspond exactly to sites where orthogonal arrays of particles (OAPs) have been visualized by freeze-fracture electron microscopy, suggesting that MIWC may be the OAP protein.
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PMID:Localization of MIWC and GLIP water channel homologs in neuromuscular, epithelial and glandular tissues. 853 39

The aquaporins are a family of transmembrane proteins that function as molecular water channels. Recently, a mercurial-insensitive water channel [MIWC or aquaporin-4 (AQP4)] has been cloned, and its mRNA was found to be expressed strongly in kidney inner medulla and several nonrenal tissues. We prepared affinity-purified polyclonal antipeptide antibodies to AQP4 to define the regional distribution and cellular location of this water channel within the kidney. Immunoblotting of membrane fractions from different regions of the kidney revealed strongest expression in the base of the renal inner medulla, with detectable levels also in the inner medullary tip, but little or no expression in the outer medulla or cortex. Immunocytochemistry (light microscopy) revealed renal AQP4 labeling exclusively in the collecting duct principal cells, chiefly in the proximal two-thirds of the inner medullary collecting duct (IMCD). Little or no expression was seen in the outer medullary and cortical collecting ducts. Immunoelectron microscopy demonstrated AQP4 labeling of the basolateral membrane of IMCD cells, with relatively little labeling of intracellular vesicles. Differential centrifugation of inner medullary homogenates also revealed a lack of distribution to the vesicle-enriched fraction, which contains the vasopressin-regulated water channel, aquaporin-2. In contrast to aquaporin-2 and aquaporin-3, water restriction of rats did not increase the level of AQP4 expression. These results suggest a possible role for AQP4 in the basolateral exit of water from the IMCD.
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PMID:Distribution of aquaporin-4 water channel expression within rat kidney. 859 71

The mercurial insensitive water channel (MIWC, AQP-4) is a water-selective transporter expressed at the basolateral plasma membrane of principal cells in kidney collecting duct, airway epithelium, and gastric parietal cells, as well as in astrocytes and skeletal muscle plasmalemma. Because these sites correspond to membranes where orthogonal arrays of particles (OAPs) have been observed by freeze-fracture electron microscopy, we tested the hypothesis that MIWC forms OAPs. Chinese hamster ovary cells were stably transfected with the coding sequence of rat MIWC under a cytomegalovirus promoter. Immunostaining of clonal cell populations showed MIWC expression at the plasma membrane. A single band at 31 kDa was detected on immunoblot. Cell fractionation by sucrose gradient centrifugation indicated strong MIWC expression in plasma membrane fractions with lesser expression in Golgi. Functional analysis by stopped-flow light scattering showed high mercurial insensitive water permeability in plasma membrane vesicles. Freeze-fracture electron microscopy showed distinct OAPs on the plasma membrane P-face of MIWC-expressing cells with morphology indistinguishable from that in basolateral membrane of kidney collecting duct; the E-face showed corresponding linear grooves (spacing, approximately 8 nm) in transfected cells and collecting duct. OAPs were not observed in control (empty vector-transfected) cells or CHIP28 (AQP1)-transfected cells in which disorganized intramembrane particle aggregates were found. These results provide direct evidence that a molecular water channel can spontaneously assemble in regular arrays.
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PMID:The mercurial insensitive water channel (AQP-4) forms orthogonal arrays in stably transfected Chinese hamster ovary cells. 861 13

A 1.8-kb cDNA clone (designed hKID, gene symbol AQP2L) with homology to the aquaporins was isolated from a human kidney cDNA library. The longest open reading frame of 846 bp encoded a 282-amino-acid hydrophobic protein that contained the conserved NPA motifs of MIP family members. Cell-free translation produced a nonglycosylated protein migrating at 29 kDa. Amino acid alignment showed the greatest homology of hKID to human MIP (48% identity) and AQP-2 (52%), with lesser homology to human MIWC (AQP-4, 34%), CHIP28 (AQP-1, 38%), and GLIP (AQP-3, 22%). Northern blot analysis revealed a 2.2-kb transcript expressed only in human kidney. PCR/Southern blot analysis of human kidney cDNA using primers flanking the hKID coding sequence revealed expression of a full-length mRNA and short transcripts with partial exon 1 and partial exon 4 deletions. Expression of hKID cRNA in Xenopus oocytes did not increase glycerol or urea permeability, but increased osmotic water permeability from (2.8 +/- 0.5) x 10(-4) to (7.4 +/- 0.7) x 10(-4) cm/s (10 degrees C) in a mercurial-sensitive manner. Sequence comparison of hKID cDNA with a cloned 21-kb genomic DNA indicated three introns (lengths 0.7, 0.25, and 0.4 kb) separating four exons with boundaries at amino acids 121, 174, and 201. The hKID promoter was identified and contained TATA, SP1, E-box, and AP1 and AP2 elements; primer extension revealed hKID transcription initiation 654 bp upstream from the translational initiation site. Genomic Southern blot indicated a single-copy hKID gene. PCR analysis of a human/rodent somatic hybrid panel localized the hKID gene to chromosome 12. Chromosomal fluorescence in situ hybridization mapped the hKID (AQP2L) gene to chromosome locus 12q13, the same location as the AQP. 2 and MIP genes. The high sequence homology, similar genomic structure, and identical chromosomal loci of hKID, MIP, and AQP-2 suggest a MIP family gene cluster at chromosome locus 12q13. Further work is needed to establish the physiological significance of hKID.
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PMID:cDNA cloning and gene structure of a novel water channel expressed exclusively in human kidney: evidence for a gene cluster of aquaporins at chromosome locus 12q13. 881 90