| 1992 |
CHIP28 (AQP1) functions as a water channel: Xenopus oocytes injected with CHIP28 RNA showed increased osmotic water permeability, reversibly inhibited by mercuric chloride, establishing CHIP28 as a functional membrane water channel. |
Xenopus oocyte expression system, osmotic swelling assay, mercurial inhibition |
Science |
High |
1373524
|
| 1992 |
Purified CHIP28 (AQP1) reconstituted into proteoliposomes exhibits up to 50-fold higher osmotic water permeability than control liposomes, without increased urea or proton permeability, demonstrating that CHIP28 itself is the functional unit of the erythrocyte water channel. |
Protein purification from human RBCs, reconstitution into proteoliposomes, stopped-flow osmotic permeability assay, mercurial inhibition |
Biochemistry |
High |
1510932
|
| 1992 |
CHIP28 (AQP1) is the erythrocyte water channel: stripping erythrocyte membranes of nearly all proteins except CHIP28 retained high water permeability; proteoliposomes reconstituted with solubilized CHIP28 had high Pf with low activation energy (~2.2 kcal/mol), inhibited by mercurials, and excluded urea. Single-channel water permeability ~10^-13 cm3/s. |
Membrane protein stripping, proteoliposome reconstitution, osmotic permeability measurement, N-terminal sequence analysis |
The Journal of biological chemistry |
High |
1526967
|
| 1993 |
Cysteine 189 is the mercury-sensitive residue in CHIP28 (AQP1): site-directed mutagenesis of each of the four cysteines (87, 102, 152, 189) to serine showed that only C189S mutant was resistant to HgCl2 inhibition. Individual CHIP28 subunits in a tetramer function independently as water pores. Residue 189 is also critical for proper protein processing. |
Site-directed mutagenesis, Xenopus oocyte expression, osmotic swelling assay, HgCl2 inhibition, immunoblot glycosylation analysis |
The Journal of biological chemistry |
High |
7677994
|
| 1993 |
CHIP28 (AQP1) assembles as tetramers in membranes: freeze-fracture EM of CHIP28-reconstituted proteoliposomes, CHIP28-transfected CHO cells, and rat kidney tubules revealed intramembrane particles (~8.5 nm diameter) composed of four subunits around a central depression. Predicted single-channel Pf of 3.6×10^-14 cm3/s at 10°C was consistent with measured tissue Pf values. |
Freeze-fracture electron microscopy, rotary shadowing, osmotic water permeability measurement in CHO cells and kidney tubules |
The Journal of cell biology |
High |
7693713
|
| 1993 |
CHIP28 (AQP1) localizes to apical brush-border and basolateral membranes throughout proximal convoluted and straight tubules and descending thin limbs of Henle in rat kidney, comprising 3.8% of isolated proximal tubule brush border protein. CHIP28 is absent from ascending thin limbs, thick ascending limbs, distal tubules, and collecting duct, correlating precisely with constitutively high water permeability segments. |
Immunolocalization by light and electron microscopy, Western blotting/quantitative immunochemistry on isolated nephron segments |
The Journal of cell biology |
High |
7678419
|
| 1993 |
Rat kidney CHIP28k (AQP1 ortholog with 94% identity to human CHIP28) functions as a selective water channel: expression in Xenopus oocytes increased Pf ~8-fold; not permeable to ions. Antisense cRNA blocked the cortical kidney mRNA-induced Pf increase. Apical membrane vesicles from proximal tubule had high water but low urea and proton permeabilities, enriching a 28-kDa protein 25-fold. |
cDNA cloning, Xenopus oocyte expression, two-electrode voltage clamp, in situ hybridization, antisense suppression, membrane vesicle reconstitution |
The Journal of cell biology |
High |
8421053
|
| 1993 |
Secondary structure of purified functional CHIP28 (AQP1) consists of ~40% alpha-helix and ~43% beta-sheet/-turn by CD and FTIR spectroscopy. HgCl2 inhibition of water transport does not alter the CD spectrum, indicating mercury acts without global protein unfolding. |
CD spectroscopy, FTIR spectroscopy, proteoliposome reconstitution |
Biochemistry |
Medium |
8218256
|
| 1993 |
CHIP28 (AQP1) localizes to apical brush-border and basolateral membranes of proximal tubule S2/S3 segments and descending thin limbs in rat kidney; also present in subapical vesicles and vasa recta endothelium. Absent from ascending limbs, thick ascending limb, distal convoluted tubule. |
Immunocytochemistry on rat kidney sections, Western blotting of kidney fractions |
The American journal of physiology |
High |
1282299
|
| 1993 |
CHIP28 (AQP1) is expressed in brush-border and basolateral membranes of nonciliated cells of the efferent duct (male reproductive tract), which shows constitutively high fluid reabsorption. Ciliated cells in the same epithelium lack CHIP28. Also found in ampulla of vas deferens, seminal vesicles, and prostate. |
Western blotting, indirect immunofluorescence, protein A-gold immunolabeling, freeze-fracture EM |
European journal of cell biology |
Medium |
8223717
|
| 1994 |
CHIP28 (AQP1) spans the membrane four times (not six or seven as hydropathy predicts): topology mapping using chimeric reporters inserted at nine positions in the CHIP28 coding region showed only four transmembrane helices, with residues 52-68 and 143-157 residing on lumenal and cytosolic ER surfaces respectively. A second internal signal sequence (residues 155-186) re-initiates translocation of a C-terminal domain into the ER lumen. |
Chimeric protein topology mapping in Xenopus oocytes, protease sensitivity assay, cell-free translation of truncated cDNAs, N-linked glycosylation at engineered sites, epitope tagging |
The Journal of cell biology |
High |
7514605
|
| 1994 |
CHIP28 (AQP1) monomers within the tetrameric complex function independently as water channels: wild-type/non-functional heterodimers (CHIP28-C189W) showed Pf proportional to the wild-type subunit contribution; wild-type/mercurial-insensitive heterodimers (CHIP28-C189S) showed ~44% inhibition by HgCl2, consistent with exactly one sensitive subunit per dimer. |
Chimeric cDNA dimer construction, Xenopus oocyte expression, osmotic swelling assay, quantitative immunofluorescence for plasma membrane expression, HgCl2 inhibition |
The Journal of biological chemistry |
High |
7511600
|
| 1994 |
CHIP28 (AQP1) is widely distributed in extrarenal epithelial and endothelial cells: immunostaining detected AQP1 in lung alveoli, bronchial mucosa and glands, choroid plexus, ciliary body, iris, lens surface, colonic crypt, sweat gland, pancreatic acini, gallbladder epithelium, placental syncytiotrophoblast, and vascular endothelium across multiple tissues. |
In situ hybridization, immunohistochemistry on rat and human tissues, Northern blot, immunoblot |
The American journal of physiology |
Medium |
7513954
|
| 1994 |
Projection structure of CHIP28 (AQP1) at 12 Å resolution from 2D crystals in lipid bilayers: tetragonal lattice (a=b=99.2 Å), plane group p4g, with four CHIP28 dimers per unit cell. Tetrameric arrangement around 4-fold axes with central stain exclusion consistent with a pore region. |
2D crystallization in synthetic lipid bilayers, low-dose electron microscopy, Fourier transform image analysis |
Biochemistry |
Medium |
7524655
|
| 1995 |
AQP1 provides a pathway for small polyols including glycerol and ethylene glycol but excludes urea, meso-erythritol, and larger polyols: osmotic swelling assay in AQP1-injected oocytes and AQP1 proteoliposomes showed significant glycerol permeability inhibited by pCMBS and CuSO4. Glycerol reflection coefficient (0.74-0.80) indicates water and glycerol share the same pathway. |
Xenopus oocyte expression, osmotic swelling assay, tritiated glycerol uptake, stopped-flow light scattering in proteoliposomes, mercurial and copper inhibition |
Pflugers Archiv : European journal of physiology |
Medium |
7491270
|
| 1995 |
CHIP28 (AQP1) secondary structure contains approximately 36% alpha-helix and 42% beta-sheet by FTIR; over 80% of peptide groups undergo hydrogen-deuterium exchange within 5 min, an exceptionally high rate consistent with a large aqueous pore within the protein structure. |
FTIR spectroscopy in H2O and 2H2O, hydrogen-deuterium exchange kinetics |
European journal of biochemistry |
Medium |
7588813
|
| 2002 |
AQP1 expressed in Xenopus oocytes increases membrane CO2 permeability, suggesting AQP1 may facilitate CO2 transport in addition to water. However, data from AQP1 reconstituted into liposomes and from AQP1 knockout mice appear inconsistent with a major CO2 transport role in those preparations. |
Xenopus oocyte expression, CO2 permeability measurement, AQP1 knockout mouse studies, liposome reconstitution |
The Journal of physiology |
Low |
12096045
|
| 2003 |
Hypertonicity-induced AQP1 expression in renal medullary cells requires activation of all three MAPK pathways (ERK, p38, and JNK) and a hypertonicity-response element in the AQP1 promoter: pharmacological inhibition of MEK1/2, MKK3/6, or MKK4 (upstream kinases for ERK, p38, JNK respectively) attenuated hypertonic induction of AQP1, and dominant-negative JNK1/2 significantly reduced AQP1 promoter activity. |
Pharmacological kinase inhibitors (U0126, SB203580, SP600125), dominant-negative kinase mutant overexpression, AQP1 promoter reporter assay, Western blot |
The Journal of biological chemistry |
Medium |
12600999
|
| 2006 |
AQP1 does not play a major role in CO2 transport in red cell ghost membranes: stopped-flow measurements of CO2 transport kinetics showed no significant difference between CO(null) human variants (lacking AQP1) and controls, or between AQP1 knockout and wild-type mice. AQP1 absence did reduce NH3 transport rates by ~30%, which was attributed to an indirect effect on RhAG-mediated transport. |
Stopped-flow fluorimetry measuring intracellular pH changes in erythrocyte ghosts from human AQP1-null variants (CO(null)) and AQP1 knockout mice |
Transfusion clinique et biologique |
Medium |
16574458
|
| 2005 |
AQP1 localizes to both apical and basolateral membranes of mouse gallbladder epithelial cells, as well as subapical vesicles, whereas AQP8 is restricted to the apical membrane. This dual-membrane localization supports AQP1 as the primary basolateral pathway for transcellular water movement in gallbladder epithelium. |
RT-PCR, immunoblotting, immunohistochemistry on mouse gallbladder epithelium |
Biology of the cell |
Medium |
15859952
|
| 2010 |
AQP1 expression is induced in reactive astrocytes following cortical stab wound injury in vivo and can be mimicked in vitro by scratch injury; this induction is blocked by MEK1/2 inhibitor U0126, placing AQP1 upregulation downstream of the MAPK/ERK signaling pathway in injury-reactive astrocytes. |
Cortical stab wound in vivo model, in vitro scratch injury assay, pharmacological MEK inhibition (U0126), immunostaining, Western blot |
Glia |
Medium |
19610096
|
| 2013 |
AQP1 mediates fast water transport in Schwann cells and controls cell volume: lentiviral knockdown of AQP1 caused cell shrinkage while overexpression caused cell swelling. AQP1 knockdown protected against hypoxia-induced edema. Hypoxic induction of AQP1 occurs in a HIF-1α-dependent manner: HIF-1α knockdown reduced hypoxia-induced AQP1 expression at both mRNA and protein levels. |
Lentiviral shRNA knockdown and overexpression, cell volume measurement, hypoxia model, HIF-1α knockdown, Western blot, qPCR |
Neuroscience |
Medium |
23948641
|
| 2015 |
AQP1 knockdown in osteosarcoma cells (U2OS, MG63) inhibited cell proliferation, induced G1 arrest and apoptosis, and reduced cell adhesion and invasion. AQP1 silencing suppressed TGF-β1/TGF-β2, RhoA, and LAMB2 expression, placing AQP1 upstream of TGF-β signaling and focal adhesion pathways in osteosarcoma cells. |
RNAi-mediated gene silencing, flow cytometry (cell cycle, apoptosis), cell adhesion and invasion assays, in vivo tumor growth in nude mice, Western blot, real-time PCR, GSEA |
Cancer biology & therapy |
Medium |
26176849
|
| 2019 |
AQP1 knockout mice show attenuation of hypoxic pulmonary hypertension: Aqp1 deficiency reduced right ventricular systolic pressure and pulmonary vascular remodeling. In vitro, Aqp1 deletion reduced hypoxia-induced proliferation, apoptosis resistance, and migration of pulmonary artery smooth muscle cells and repressed HIF-1α protein stability. AQP1 loss also protected lung endothelial cells from hypoxic apoptosis. |
AQP1 knockout mouse model, right ventricular pressure measurement, histomorphometry, primary cell culture, cell cycle/apoptosis/migration assays, Western blot for HIF-1α |
Arteriosclerosis, thrombosis, and vascular biology |
Medium |
30580569
|
| 2019 |
Both AQP1 and AQP4 contribute to cerebrospinal fluid production: AQP1 knockout, AQP4 knockout, and double knockout mice all showed significantly altered intraventricular pressure and CSF outflow compared to wild-type controls. Double knockout additionally altered ventricular compliance and CSF drainage, revealing additive roles for AQP1 in CSF homeostasis. |
Intraventricular pressure recording, CSF outflow measurement, MRI ventricular volume quantification in single and double AQP knockout mice |
Cells |
Medium |
30813473
|
| 2020 |
AQP1 expression declines with tendon aging; AQP1 overexpression in aged tendon stem/progenitor cells (TSPCs) attenuated senescence, restored self-renewal, migration, and tenogenic differentiation. Mechanistically, aged TSPCs showed activated JAK-STAT signaling, and AQP1 overexpression inhibited JAK-STAT pathway activation, placing AQP1 as a negative regulator of JAK-STAT-driven senescence. |
Lentiviral overexpression of AQP1 in aged TSPCs, senescence assays, migration and differentiation assays, Western blot for JAK-STAT pathway components |
Cell death & disease |
Medium |
32188840
|
| 2021 |
The AQP1 promoter variant rs2075574 reduces AQP1 promoter activity, AQP1 protein expression, and glucose-driven osmotic water transport across the peritoneal membrane, mechanistically linking reduced AQP1 expression to impaired peritoneal ultrafiltration in dialysis patients. |
AQP1 promoter activity reporter assay, AQP1 expression measurement in cells and human samples, osmotic water transport assay, clinical genetic association in 1851 patients |
The New England journal of medicine |
High |
34670044
|
| 2024 |
AQP1 deficiency exacerbates phthalate (DEHP)-induced duodenal epithelial barrier disruption: DEHP directly inhibits AQP1 expression, leading to activation of the TLR4/MyD88/NF-κB inflammatory signaling pathway and disruption of intestinal integrity. AQP1 is thus mechanistically placed as a suppressor of TLR4/MyD88/NF-κB activation in intestinal epithelium. |
DEHP exposure in vivo and in vitro, AQP1 expression analysis, inflammatory pathway Western blot and gene expression, barrier function assays, mitochondrial morphology assessment |
Journal of agricultural and food chemistry |
Low |
38916549
|