A refined structure of human aquaporin‐1

Groot, Bert L. de; Engel, Andréas; Grubmüller, Helmut

doi:10.1016/s0014-5793(01)02743-0

Cited by 132 publications

(133 citation statements)

References 39 publications

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“…4), we conclude that the 4-to 6-nm IMPs and pits represent individual AQP4 tetramers. This conclusion is supported by atomic structures of homologous proteins AQP1 (20,32,33) and GlpF (34), with tetramer cross-sectional diameters of 6 nm. The slightly smaller diameter of the replicated IMPs and pits may reflect the diameter of each tetramer within the lipid bilayer.…”

Section: Discussionmentioning

confidence: 83%

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Aquaporin-4 square array assembly: Opposing actions of M1 and M23 isoforms

Furman

Gorelick-Feldman

Davidson

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

286

287

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Osmotic homeostasis in the brain involves movement of water through aquaporin-4 (AQP4) membrane channels. Perivascular astrocyte end-feet contain distinctive orthogonal lattices (square arrays) assembled from 4-to 6-nm intramembrane particles (IMPs) corresponding to individual AQP4 tetramers. Two isoforms of AQP4 result from translation initiation at methionine residues M1 and M23, but no functional differences are known. In this study, Chinese hamster ovary cells were transfected with M1, M23, or M1؉M23 isoforms, and AQP4 expression was confirmed by immunoblotting, immunocytochemistry, and immunogold labeling. Square array organization was examined by freeze-fracture electron microscopy. In astrocyte end-feet, >90% of 4-to 6-nm IMPs were found in square arrays, with 65% in arrays of 13-30 IMPs. In cells transfected with M23, 95% of 4-to 6-nm IMPs were in large assemblies (rafts), 85% of which contained >100 IMPs. However, in M1 cells, >95% of 4-to 6-nm IMPs were present as singlets, with <5% in incipient arrays of 2-12 IMPs. In A quaporins are specialized water transport channels in plasma membranes of water-permeable tissues (1). Aquaporins 1 and 4 (AQP1 and AQP4) are most important to fluid movements in mammalian brain. AQP4 exists as two isoforms, differing at their N termini, because of translation initiation at the first methionine (M1, 323 aa) or the second methionine (M23, 301 aa) (2, 3). Both isoforms are present in brain, but M23 is at least 3-fold more abundant (4, 5). Endogenous AQP4 is a tetramer usually containing M1 and M23 subunits. The water permeabilities of M1 and M23 are similar, and functional differences are not known (3, 4).Fluid movements are precisely orchestrated within the rigid cranium to prevent physical damage from swelling or shrinkage. Interfaces between brain parenchyma and cerebrospinal fluid occur around the ventricles, surrounding blood vessels, and at the brain surface. AQP1 is expressed in rat choroid plexus, the site of cerebrospinal fluid secretion (6), whereas AQP4 is enriched in rat astrocyte end-feet surrounding brain capillaries (7,8). Astrocyte processes forming the glia limitans at brain surfaces, ependymal cells lining brain ventricles, and Müller cells facing the vitreous body and retinal blood vessels all have abundant AQP4 (9). AQP4 in perivascular membranes of astrocyte end-feet has been implicated in neurological disorders, including acute hyponatremic edema, postischemic injury, and epileptic seizures (10-13).Perivascular membranes of astrocyte end-feet contain numerous strikingly regular arrays of intramembrane particles (IMPs) in freeze-fracture electron micrographs. These IMP arrays have been referred to as square arrays, assemblies, or orthogonally arranged particles (OAPs) (14). In early freeze-fracture images of astrocyte end-feet (15), square arrays were resolved as 6-nm IMP protrusions in P-face images (protoplasmic leaflets) or as smaller pits in E-faces (extraplasmic leaflets). The sizes and shapes of square arrays vary, but the IMPs and pits have un...

show abstract

Section: Discussionmentioning

confidence: 83%

“…M23 and M1 polypeptides are identical except the 22-residue peptide at the N terminus of M1. It is unknown how this additional segment interferes with square array assembly, because the atomic structures of homologous proteins did not resolve N and C termini (20,(32)(33)(34).…”

Section: Discussionmentioning

confidence: 99%

Aquaporin-4 square array assembly: Opposing actions of M1 and M23 isoforms

Furman

Gorelick-Feldman

Davidson

et al. 2003

Proc. Natl. Acad. Sci. U.S.A.

286

287

View full text Add to dashboard Cite

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“…MIP channels comprise water channels (aquaporins) and glycerol facilitators (aquaglyceroporins) (17). Water channels are highly specific to water (17,21,22), although transport of ions has also been reported (23,24). Glycerol facilitators commonly transport small polyols and a range of other uncharged molecules (25), and apparently even metalloid ions (26,27).…”

mentioning

confidence: 99%

“…Glycerol facilitators commonly transport small polyols and a range of other uncharged molecules (25), and apparently even metalloid ions (26,27). The three-dimensional structure of human aquaporin AQP1 and of the E. coli glycerol facilitator GlpF have been determined (21,22,25,28). MIP channels consist of six transmembrane domains (TMDs) comprised of an internal repeat of three TMDs.…”

mentioning

confidence: 99%

A Short Regulatory Domain Restricts Glycerol Transport through Yeast Fps1p

Tamás

Karlgren

Bill

et al. 2003

Journal of Biological Chemistry

116

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The controlled export of solutes is crucial for cellular adaptation to hypotonic conditions. In the yeast Saccharomyces cerevisiae glycerol export is mediated by Fps1p, a member of the major intrinsic protein (MIP) family of channel proteins. Here we describe a short regulatory domain that restricts glycerol transport through Fps1p. This domain is required for retention of cellular glycerol under hypertonic stress and hence acquisition of osmotolerance. It is located in the N-terminal cytoplasmic extension close to the first transmembrane domain. Several residues within that domain and its precise position are critical for channel control while the proximal residues 13-215 of the N-terminal extension are not required. The sequence of the regulatory domain and its position are perfectly conserved in orthologs from other yeast species. The regulatory domain has an amphiphilic character, and structural predictions indicate that it could fold back into the membrane bilayer. Remarkably, this domain has structural similarity to the channel forming loops B and E of Fps1p and other glycerol facilitators. Intragenic second-site suppressor mutations of the sensitivity to high osmolarity conferred by truncation of the regulatory domain caused diminished glycerol transport, confirming that elevated channel activity is the cause of the osmosensitive phenotype.

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“…Aquaporins are remarkably efficient water channels, yet are strikingly selective against ions and even protons. Recent molecular dynamics simulations of water permeation through the channels (15,16) have revealed how these somewhat contradictory properties have been simultaneously optimized.…”

mentioning

confidence: 99%

A refined structure of human aquaporin‐1

Cited by 132 publications

References 39 publications

Aquaporin-4 square array assembly: Opposing actions of M1 and M23 isoforms

Aquaporin-4 square array assembly: Opposing actions of M1 and M23 isoforms

A Short Regulatory Domain Restricts Glycerol Transport through Yeast Fps1p

What happens if the room at the bottom runs out? A close look at small water pores

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