Evidence map›Paper›PMID 22987455›Full record

ArticleGlia2012

Neuromyelitis optica IgG does not alter aquaporin-4 water permeability, plasma membrane M1/M23 isoform content, or supramolecular assembly.

Andrea Rossi, Julien Ratelade, Marios C Papadopoulos, Jeffrey L Bennett, A S Verkman

Open access · greenAbstract read
In one paragraph

Article in Glia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.

0numbers the graph read from it
0cells of the map it votes in
42citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

42 citing papers in PubMed, 57 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Aquaporins in Nervous System.Advances in experimental medicine and biology · 2023
    Article
  7. Article
  8. Review
  9. Article
  10. Review
  11. Review
  12. Article
  13. Article
  14. Neuromyelitis Optica: Deciphering a Complex Immune-Mediated Astrocytopathy.Journal of neuro-ophthalmology : the official journal of the North American Neuro-Ophthalmology Society · 2017
    Review
  15. Article
  16. Article
  17. Article
  18. Article
  19. Aquaporin-Targeted Therapeutics: State-of-the-Field.Advances in experimental medicine and biology · 2017
    Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 3 institutions in 2 countries.

Andrea RossiDepartment of Medicine, University of California, San Francisco, California 94143, USA.
Julien Ratelade
Marios C Papadopoulos
Jeffrey L Bennett
A S Verkman
University of California, San Francisco · USSt George's, University of London · GBUniversity of Colorado Denver · US

Funding

SynthesisP30DK072517 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2005 to 2022
$18.1M
Functional Role of Aquaporins in Eye PhysiologyR01EY013574 · NEI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2002 to 2022
$7.6M
MECHANISMS OF WATER TRANSPORT IN RENAL EPITHELIAR37DK035124 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 1999 to 2008
$4.2M
Application of Novel Optical Methods to Cell DynamicsR37EB000415 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2007 to 2016
$4.1M
Role of ASL and Airway Glands in CF Lung DiseaseR01HL073856 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2003 to 2010
$3.1M
Application of Novel Optical Methods to Cell DynamicsR01EB000415 · NIBIB · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2002 to 2006
$1.7M
WATER AND NON-ELECTROLYTE TRANSPORT IN RENAL VESICLESR01DK035124 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 1986 to 2014
$1.4M
CFTR inhibitors for therapy of polycystic kidney diseaseRC1DK086125 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI VERKMAN, ALAN S · 2009 to 2010
$989k
NEI NIH HHS EY13574NEI NIH HHS R01 EY013574NHLBI NIH HHS HL73856NHLBI NIH HHS R01 HL073856NIBIB NIH HHS EB00415NIBIB NIH HHS R01 EB000415NIBIB NIH HHS R37 EB000415NIDDK NIH HHS DK35124NIDDK NIH HHS DK72517NIDDK NIH HHS DK86125NIDDK NIH HHS P30 DK072517NIDDK NIH HHS R01 DK035124NIDDK NIH HHS R37 DK035124NIDDK NIH HHS RC1 DK086125
6 · The paper itself

Abstract

Neuromyelitis optica (NMO) is thought to be caused by immunoglobulin G autoantibodies (NMO-IgG) against astrocyte water channel aquaporin-4 (AQP4). A recent study (Hinson et al. (2012) Proc Natl Acad Sci USA 109:1245-1250) reported that NMO-IgG inhibits AQP4 water permeability directly and causes rapid cellular internalization of the M1 but not M23 isoform of AQP4, resulting in AQP4 clustering, enhanced complement-dependent cytotoxicity, and tissue swelling. Here, we report evidence challenging this proposed mechanism of NMO-IgG-mediated pathology. We measured osmotic water permeability by stopped-flow light scattering on plasma membrane vesicles isolated from AQP4-expressing CHO cells, an approach that can detect changes in water permeability as small as 5% and is not confounded by internalization effects. We found similar single-molecule water permeability for M1-AQP4 tetramers and M23-AQP4 clusters (orthogonal arrays of particles, OAPs). Exposure of AQP4 to high concentrations of NMO-IgG from six seropositive NMO patients, and to high-affinity recombinant monoclonal NMO antibodies, did not reduce AQP4 water permeability. Also, NMO-IgG did not reduce water permeability in AQP4-reconstituted proteoliposomes. In transfected cells expressing M1- or M23-AQP4 individually, NMO-IgG caused more rapid internalization of M23- than M1-AQP4. In cells coexpressing both isoforms, M1- and M23-AQP4 comingled in OAPs that were internalized together in response to NMO-IgG. Super-resolution imaging and native gel electrophoresis showed that the size of AQP4 OAPs was not altered by NMO sera or recombinant NMO antibodies. We conclude that NMO-IgG does not: (i) inhibit AQP4 water permeability, (ii) cause preferential internalization of M1-AQP4, or (iii) cause intramembrane AQP4 clustering.

Indexed as

AnimalsAntibodies, MonoclonalAquaporin 4AutoantibodiesCell Line, TumorCell MembraneCell Membrane PermeabilityCHO CellsCricetinaeCricetulusHumansImmunoglobulin GMultiprotein ComplexesNeuromyelitis OpticaProtein BindingProtein IsoformsAntibodies, MonoclonalAQP4 protein, humanAquaporin 4AutoantibodiesImmunoglobulin GMultiprotein ComplexesProtein IsoformsWater

Identifiers

PMID22987455
PMCPMC3586219
OpenAlexW2067325343

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.