An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain

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dc.contributor.author Traystman, R J
dc.contributor.author Haug, F M
dc.contributor.author Agre, P
dc.contributor.author Amiry-Moghaddam, M
dc.contributor.author Froehner, S C
dc.contributor.author Adams, M E
dc.contributor.author Hurn, P D
dc.contributor.author Ottersen, O P
dc.contributor.author Otsuka, T
dc.contributor.author Neely, J D
dc.contributor.author Bhardwaj, A
dc.date.accessioned 2010-03-04T19:41:14Z
dc.date.available 2010-03-04T19:41:14Z
dc.date.issued 2003-02-18
dc.identifier.citation Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2106-11. Epub 2003 Feb 10. http://www.pnas.org/content/100/4/2106.full en
dc.identifier.uri http://jhir.library.jhu.edu/handle/1774.2/33881
dc.description.abstract The water channel AQP4 is concentrated in perivascular and subpial membrane domains of brain astrocytes. These membranes form the interface between the neuropil and extracerebral liquid spaces. AQP4 is anchored at these membranes by its carboxyl terminus to alpha-syntrophin, an adapter protein associated with dystrophin. To test functions of the perivascular AQP4 pool, we studied mice homozygous for targeted disruption of the gene encoding alpha-syntrophin (alpha-Syn(-/-)). These animals show a marked loss of AQP4 from perivascular and subpial membranes but no decrease in other membrane domains, as judged by quantitative immunogold electron microscopy. In the basal state, perivascular and subpial astroglial end-feet were swollen in brains of alpha-Syn(-/-) mice compared to WT mice, suggesting reduced clearance of water generated by brain metabolism. When stressed by transient cerebral ischemia, brain edema was attenuated in alpha-Syn(-/-) mice, indicative of reduced water influx. Surprisingly, AQP4 was strongly reduced but alpha-syntrophin was retained in perivascular astroglial end-feet in WT mice examined 23 h after transient cerebral ischemia. Thus alpha-syntrophin-dependent anchoring of AQP4 is sensitive to ischemia, and loss of AQP4 from this site may retard the dissipation of postischemic brain edema. These studies identify a specific, syntrophin-dependent AQP4 pool that is expressed at distinct membrane domains and which mediates bidirectional transport of water across the brain-blood interface. The anchoring of AQP4 to alpha-syntrophin may be a target for treatment of brain edema, but therapeutic manipulations of AQP4 must consider the bidirectional water flux through this molecule. en
dc.description.provenance Submitted by Janice Chen (janice.chen@jhu.edu) on 2010-03-04T17:50:43Z No. of bitstreams: 1 PNAS-2003-Amiry-Moghaddam-2106-11.pdf: 499441 bytes, checksum: f5fbda4c97629f89f94a6663d6338b52 (MD5) en
dc.description.provenance Made available in DSpace on 2010-03-04T19:41:14Z (GMT). No. of bitstreams: 1 PNAS-2003-Amiry-Moghaddam-2106-11.pdf: 499441 bytes, checksum: f5fbda4c97629f89f94a6663d6338b52 (MD5) Previous issue date: 2003-02-18 en
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dc.language.iso en_US en
dc.publisher National Academy of Sciences en
dc.subject Aquaporins/metabolism en
dc.subject Membrane Proteins/metabolism en
dc.subject Body Water en
dc.subject Astrocytes/metabolism en
dc.subject Muscle Proteins/metabolism en
dc.title An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain en
dc.title.alternative An α-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain en
dc.type Article en

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