| Evidences for a leaky scanning mechanism for the synthesis of the shorter M23 protein isoform of aquaporin-4: implication in orthogonal array formation and neuromyelitis optica antibody interaction. | |
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MedLine Citation:
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PMID: 20007705 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Aquaporin-4 (AQP4) exists as two major isoforms that differ in the length of the N terminus, the shorter AQP4-M23 and the longer AQP4-M1. Both isoforms form tetramers, which can further aggregate in the plasma membrane to form typical orthogonal arrays of particles (OAPs) whose dimension depends on the ratio of the M1 and M23. In this study, we tested the hypothesis that the M23 isoform can be produced directly by the M1 mRNA. In cells transiently transfected with AQP4-M1 coding sequence we observed besides AQP4-M1 the additional presence of the AQP4-M23 isoform associated with the formation of typical OAPs observable by two-dimensional blue native/SDS-PAGE and total internal reflection microscopy. The mutation of the second in-frame methionine M23 in AQP4-M1 (AQP4-M1(M23I)) prevented the expression of the M23 isoform and the formation of OAPs. We propose "leaky scanning" as a translational mechanism for the expression of AQP4-M23 protein isoform and that the formation of OAPs may occur even in the absence of AQP4-M23 mRNA. This mechanism can have important pathophysiological implications for the cell regulation of the M1/M23 ratio and thus OAP size. In this study we also provide evidence that AQP4-M1 is mobile in the plasma membrane, that it is inserted and not excluded into immobile OAPs, and that it is an important determinant of OAP structure and size. |
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Authors:
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Andrea Rossi; Francesco Pisani; Grazia Paola Nicchia; Maria Svelto; Antonio Frigeri |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-12-10 |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 285 ISSN: 1083-351X ISO Abbreviation: J. Biol. Chem. Publication Date: 2010 Feb |
Date Detail:
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Created Date: 2010-02-08 Completed Date: 2010-05-11 Revised Date: 2011-07-25 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: United States |
Other Details:
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Languages: eng Pagination: 4562-9 Citation Subset: IM |
Affiliation:
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Department of General and Environmental Physiology and Centre of Excellence in Comparative Genomics, University of Bari, Bari 70125, Italy. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aquaporin 4
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genetics,
metabolism* Blotting, Western Cell Membrane / metabolism Electrophoresis, Polyacrylamide Gel Fluorescence Recovery After Photobleaching Fluorescent Antibody Technique Hela Cells Humans Microscopy, Fluorescence Mutation Protein Isoforms / genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/AQP4 protein, human; 0/Aquaporin 4; 0/Protein Isoforms |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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