Dystrophin-associated protein scaffolding in brain requires alpha-dystrobrevin.
Dystrophin and the alpha-dystrobrevins bind directly to the adapter protein syntrophin to form membrane-associated scaffolds. At the blood-brain barrier, alpha-syntrophin colocalizes with dystrophin and the alpha-dystrobrevins in perivascular glial endfeet and is required for localization of the water channel aquaporin-4. Earlier we have shown that localization of the scaffolding proteins gamma2-syntrophin, alpha-dystrobrevin-2, and dystrophin to glial endfeet is also dependent on the presence of alpha-syntrophin. In this study, we show that the expression levels of alpha-syntrophin, gamma2-syntrophin, and dystrophin at the blood-brain barrier are reduced in alpha-dystrobrevin-null mice. This is the first demonstration in which assembly of an astroglial protein scaffold containing syntrophin and dystrophin in perivascular astrocytes is dependent on the presence of alpha-dystrobrevin.
Bragg
April D
AD
Department of Physiology and Biophysics, University of Washington, Seattle, Washington 98195, USA.
Das
Sonal S
SS
Froehner
Stanley C
SC
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001812:Blood-Brain Barrier / Q000378:metabolism*; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000378:metabolism; D002531:Cerebellum / Q000098:blood supply / Q000378:metabolism; D016189:Dystrophin / Q000378:metabolism*; D049029:Dystrophin-Associated Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018613:Microscopy, Confocal; D009124:Muscle Proteins / Q000378:metabolism
D002135:Calcium-Binding Proteins; D016189:Dystrophin; D049029:Dystrophin-Associated Proteins; D008565:Membrane Proteins; D009124:Muscle Proteins; C098885:dystrobrevin; C091825:syntrophin alpha1