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

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dc.contributor.author Rash, J E
dc.contributor.author Agre, P
dc.contributor.author Neely, J D
dc.contributor.author Yasumura, T
dc.contributor.author Davidson, K G
dc.contributor.author Gorelick-Feldman, D A
dc.contributor.author Furman, C S
dc.date.accessioned 2010-03-04T19:59:38Z
dc.date.available 2010-03-04T19:59:38Z
dc.date.issued 2003-11-11
dc.identifier.citation Proc Natl Acad Sci U S A. 2003 Nov 11;100(23):13609-14. Epub 2003 Nov 3. http://www.pnas.org/content/100/23/13609.abstract en
dc.identifier.uri http://jhir.library.jhu.edu/handle/1774.2/33888
dc.description.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. en
dc.description.provenance Submitted by Janice Chen (janice.chen@jhu.edu) on 2010-03-04T16:36:55Z No. of bitstreams: 1 PNAS-2003-Furman-13609-14.pdf: 1119679 bytes, checksum: b0bcc0bf46a2921ace7c1bd8a7ec3dcf (MD5) en
dc.description.provenance Approved for entry into archive by David Reynolds(davidr@jhu.edu) on 2010-03-04T19:59:38Z (GMT) No. of bitstreams: 1 PNAS-2003-Furman-13609-14.pdf: 1119679 bytes, checksum: b0bcc0bf46a2921ace7c1bd8a7ec3dcf (MD5) en
dc.description.provenance Made available in DSpace on 2010-03-04T19:59:38Z (GMT). No. of bitstreams: 1 PNAS-2003-Furman-13609-14.pdf: 1119679 bytes, checksum: b0bcc0bf46a2921ace7c1bd8a7ec3dcf (MD5) Previous issue date: 2003-11-11 en
dc.language.iso en_US en
dc.publisher National Academy of Sciences en
dc.subject Aquaporins/physiology en
dc.title Aquaporin-4 square array assembly: Opposing actions of M1 and M23 isoforms en
dc.type Article en

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