RGD Reference Report - Supramolecular aggregation of aquaporin-4 is different in muscle and brain: correlation with tissue susceptibility in neuromyelitis optica. - Rat Genome Database

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Supramolecular aggregation of aquaporin-4 is different in muscle and brain: correlation with tissue susceptibility in neuromyelitis optica.

Authors: Rosito, Stefania  Nicchia, Grazia Paola  Palazzo, Claudia  Lia, Anna  Buccoliero, Cinzia  Pisani, Francesco  Svelto, Maria  Trojano, Maria  Frigeri, Antonio 
Citation: Rosito S, etal., J Cell Mol Med. 2018 Feb;22(2):1236-1246. doi: 10.1111/jcmm.13401. Epub 2017 Oct 20.
RGD ID: 14397568
Pubmed: (View Article at PubMed) PMID:29055082
DOI: Full-text: DOI:10.1111/jcmm.13401

Neuromyelitis optica (NMO) is an autoimmune demyelinating disease of the central nervous system (CNS) caused by autoantibodies (NMO-IgG) against the water channel aquaporin-4 (AQP4). Though AQP4 is also expressed outside the CNS, for example in skeletal muscle, patients with NMO generally do not show clinical/diagnostic evidence of skeletal muscle damage. Here, we have evaluated whether AQP4 supramolecular organization is at the basis of the different tissue susceptibility. Using immunofluorescence we found that while the sera of our cohort of patients with NMO gave typical perivascular staining in the CNS, they were largely negative in the skeletal muscle. This conclusion was obtained using human, rat and mouse skeletal muscle including the AQP4-KO mouse. A biochemical analysis using a new size exclusion chromatography approach for AQP4 suprastructure fractionation revealed substantial differences in supramolecular AQP4 assemblies and isoform abundance between brain and skeletal muscle matching a lower binding affinity of NMO-IgG to muscle compared to the brain. Super-resolution microscopy analysis with g-STED revealed different AQP4 organization in native tissues, while in the brain perivascular astrocyte endfoot membrane AQP4 was mainly organized in large interconnected and raft-like clusters, in the sarcolemma of fast-twitch fibres AQP4 aggregates often appeared as small, relatively isolated linear entities. In conclusion, our results provide evidence that AQP4 supramolecular structure is different in brain and skeletal muscle, which is likely to result in different tissues susceptibility to the NMO disease.



Gene Ontology Annotations    

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Aqp4  (aquaporin 4)


Additional Information