NDLI: Aquaporin-4 square array assembly: opposing actions of M1 and M23 isoforms.

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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Yasumura, Thomas Rash, John E. Neely, John D. Davidson, Kimberly G. V. Gorelick-feldman, Daniel A. Agre, Peter Furman, C. Sue
Description	Author Affiliation: Furman CS ( Department of Biomedical Sciences and Program in Molecular, Cellular, and Integrative Neurosciences, Colorado State University, Fort Collins, CO 80523, USA.);
Abstract	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 M1+M23 cells, 4- to 6-nm IMPs were in arrays of intermediate sizes, resembling square arrays in astrocytes. Structural cross-bridges of 1 x 2 nm linked >90% of IMPs in M23 arrays ( approximately 1,000 cross-bridges per microm2) but were rarely seen in M1 cells. These studies show that M23 and M1 isoforms have opposing effects on intramembrane organization of AQP4: M23 forms large square arrays with abundant cross-bridges; M1 restricts square array assembly.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	23
Volume Number	100
Language	English
Publisher	National Academy of Sciences
Publisher Date	2003-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Aquaporins Physiology Animals Aquaporin 4 Chemistry Astrocytes Metabolism CHO Cells Cricetinae Freeze Fracturing Immunoblotting Immunohistochemistry Plasmids Protein Isoforms Transfection Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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