Identification and Structure of a Putative Ca2+-binding Domain at the C Terminus of AQP1

Fotiadis, Dimitrios; Suda, Kitaru; Tittmann, Peter; Jenö, Paul; Philippsen, Ansgar; Müller, Daniel J.; Gross, Heinz; Engel, Andréas

doi:10.1016/s0022-2836(02)00143-2

Cited by 65 publications

(54 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To identify AQP1 the immunoblots were probed with an anti-AQP1 antibody directed against the C-terminal 19 aminoacids of human AQP1 (residues 243-261: KVWTSGQVEEYDLDADDIN; UniProtKB ID: P29972), a region that is completely conserved in bovine AQP1 (residues 245-263; UniProtKB ID: P47865). Immunoblots of hRBC and bRBC, probed with anti-hAQP1, showed the presence of three bands of ~ 53, 40 and 29 kDa as previously reported for the purified forms of this protein [25]. After PNGase F treatment, in both samples (hRBC and bRBC) the bands of higher molecular mass were completely absent yielding a single band of ~ 29 kDa, which might represent the deglycosylated AQP1 as formerly reported [15].…”

Section: Bovine Erythrocytes Show Higher Glycosilated Aqp1 Expressionsupporting

confidence: 82%

Lack of Aquaporin 3 in bovine erythrocyte membranes correlates with low glycerol permeation

Campos

Moura

Oliva

et al. 2011

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

In general, erythrocytes are highly permeable to water, urea and glycerol.However, expression of aquaporin isoforms in erythrocytes appears to be species characteristic. In the present study, human (hRBC) and bovine (bRBC) erythrocytes were chosen for comparative studies due to their significant difference in membrane glycerol permeability.Osmotic water permeability (P f ) at 23 ºC was (2.89 0.37) 10 -2 and (5.12 0.61) 10 -2 cm s -1 for human and bovine cells respectively, with similar activation energies for water transport. Glycerol permeability (P gly ) for human ((1.37 0.26) 10 -5 cm s -1 ) differed in three orders of magnitude from bovine erythrocytes ((5.82 0.37) 10 -8 cm s -1 ) that also showed higher activation energy for glycerol transport.When compared to human, bovine erythrocytes showed a similar expression pattern of AQP1 glycosylated forms on immunoblot analysis, though in slight higher levels, which could be correlated with the 1.5-fold larger P f found. However, AQP3 expression was not detectable. Immunofluorescence analysis confirmed the absence of AQP3 expression in bovine erythrocyte membranes.In conclusion, lack of AQP3 in bovine erythrocytes points to the lipid pathway as responsible for glycerol permeation and explains the low glycerol permeability and high E a for transport observed in ruminants.

show abstract

Section: Bovine Erythrocytes Show Higher Glycosilated Aqp1 Expressionsupporting

confidence: 82%

Lack of Aquaporin 3 in bovine erythrocyte membranes correlates with low glycerol permeation

Campos

Moura

Oliva

et al. 2011

Biochemical and Biophysical Research Communications

View full text Add to dashboard Cite

show abstract

“…For the candidate amino acids implicated in coordinating bumetanide binding, only minor topological differences exist in site 1 between bAQP1 and rAQP4. The two residues found thus far by mutagenesis to affect AqB013 efficacy are located in intracellular loop D, which has been proposed to serve in gating AQP channel functions in mammalian AQP1 (Yu et al, 2006), AQP4 (Fotiadis et al, 2002;Zelenina et al, 2002), and plant AQP (Tornroth-Horsefield et al, 2006). For these residues, Val189 of AQP4 is Gly170 in AQP1, and Ser180 in rAQP4 is Thr158 in bAQP1, which are conservative changes.…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Aquaporin-1 and Aquaporin-4 Water Permeability by a Derivative of the Loop Diuretic Bumetanide Acting at an Internal Pore-Occluding Binding Site

et al. 2009

View full text Add to dashboard Cite

Aquaporin (AQP) water channels, essential for fluid homeostasis, are expressed in perivascular brain end-feet regions of astroglia (AQP4) and in choroid plexus (AQP1). At a high concentration, the loop diuretic bumetanide has been shown to reduce rat brain edema after ischemic stroke by blocking Na ϩ -K ϩ -2Cl Ϫ cotransport. We hypothesized that an additional inhibition of AQP contributes to the protection. We show that osmotic water flux in AQP4-expressing Xenopus laevis oocytes is reduced by extracellular bumetanide (Ն100 M). The efficacy of block by bumetanide is increased by injection intracellularly. Forty-five synthesized bumetanide derivatives were tested on oocytes expressing human AQP1 and rat AQP4. Of these, one of the most effective was the 4-aminopyridine carboxamide analog, AqB013, which inhibits AQP1 and AQP4 (IC 50 ϳ20 M, applied extracellularly). The efficacy of block was enhanced by mutagenesis of intracellular AQP4 valine-189 to alanine (V189A, IC 50 ϳ8 M), confirming the aquaporin as the molecular target of block. In silico docking of AqB013 supported an intracellular candidate binding site in rat AQP4 and suggested that the block involves occlusion of the AQP water pore at the cytoplasmic side. AqB013 at 2 M had no effect, and 20 M caused 20% block of human Na ϩ -K ϩ -2Cl Ϫ cotransporter activity, in contrast to Ͼ90% block of the transporter by bumetanide. AqB013 did not affect X. laevis oocyte Cl Ϫ currents and did not alter rhythmic electrical conduction in an ex vivo gastric muscle preparation. The identification of AQP-selective pharmacological agents opens opportunities for breakthrough strategies in the treatment of edema and other fluid imbalance disorders.

show abstract

“…Docking simulations have identified two potential intracellular binding sites in AQP4, one being positioned in the water pore vestibule whereas the second is in a separate intracellular pocket that involves residues from the C-terminus and intracellular loop (44). This second site, which has a potential for allosteric regulation of the pore, has also been associated with regulation of AQP1 by cGMP (39), protein kinase C (40) and Ca2+ (45). Recent work has identified the first known aquaporin pharmacological agonist, AqF026, a chemical derivative of the arylsulfonamide compound furosemide (46) (Fig.…”

Section: Pharmacological Agonists Of the Aquaporinsmentioning

confidence: 99%

Water transport across the peritoneal membrane

Devuyst

Rippe

2014

Kidney International

View full text Add to dashboard Cite

Peritoneal dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. The capillary endothelium offers the rate-limiting hindrance for solute and water transport. It can be functionally described in terms of a three-pore model including transcellular, ultrasmall pores responsible for free-water transport during crystalloid osmosis. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore located in endothelial cells. Studies in Aqp1 mice have shown that deletion of AQP1 is reflected by a 50% decrease in ultrafiltration and a disappearance of the sodium sieving. Haploinsufficiency in AQP1 is also reflected by a significant attenuation of water transport. Conversely, studies in a rat model and in PD patients have shown that the induction of AQP1 in peritoneal capillaries by corticosteroids is reflected by increased water transport and ultrafiltration, without affecting the osmotic gradient and small-solute transport. Recent data have demonstrated that a novel agonist of AQP1, predicted to stabilize the open-state conformation of the channel, modulates water transport and improves ultrafiltration. Whether increasing the expression of AQP1 or gating the already existing channels would be clinically useful in PD patients remains to be investigated. ABSTRACTPeritoneal dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. The capillary endothelium offers the rate-limiting hindrance for solute and water transport. It can be functionally described in terms of a threepore model including transcellular, ultrasmall pores responsible for free-water transport during crystalloid osmosis. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore located in endothelial cells. Studies in Aqp1 mice have shown that deletion of AQP1 is reflected by a 50% decrease in ultrafiltration and a disappearance of the sodium sieving. Haplo-insufficiency in AQP1 is also reflected by a significant attenuation of water transport. Conversely, studies in a rat model and in PD patients have shown that the induction of AQP1 in peritoneal capillaries by corticosteroids is reflected by increased water transport and ultrafiltration, without affecting the osmotic gradient and small solute transport. Recent data have demonstrated that a novel agonist of AQP1, predicted to stabilize the open state conformation of the channel, modulates water transport and improves ultrafiltration. Whether increasing the expression of AQP1 or gating the already existing channels would be clinically useful in PD patients remains to be investigated.The development of peritoneal dialysis (PD) as a successful therapy for patients with end stage renal disease has been paralleled by the need to understand the transport mechanisms operating in the peritoneal membrane. Functional alterations in the dialysis capacity of the...

show abstract

Identification and Structure of a Putative Ca2+-binding Domain at the C Terminus of AQP1

Cited by 65 publications

References 60 publications

Lack of Aquaporin 3 in bovine erythrocyte membranes correlates with low glycerol permeation

Lack of Aquaporin 3 in bovine erythrocyte membranes correlates with low glycerol permeation

Inhibition of Aquaporin-1 and Aquaporin-4 Water Permeability by a Derivative of the Loop Diuretic Bumetanide Acting at an Internal Pore-Occluding Binding Site

Water transport across the peritoneal membrane

Contact Info

Product

Resources

About