Dystrophin-Associated Protein Scaffolding in Brain Requires α-

Dystrophin and the α-dystrobrevins bind directly to the adaptor protein syntrophin to form membrane-associated scaffolds. At the blood-brain barrier, α-syntrophin co-localizes with dystrophin and the α-dystrobrevins in perivascular glial endfeet and is required for localization of the water channel aquaporin-4. We have previously shown that localization of the scaffolding proteins γ2-syntrophin, α-dystrobrevin-2, and dystrophin to glial endfeet is also dependent upon the presence of α-syntrophin. In the present study, we show that the expression levels of α-syntrophin, γ2-syntrophin, and dystrophin at the blood-brain barrier are reduced in α-dystrobrevin-null mice. This is the first demonstration that assembly of an astroglial protein scaffold containing syntrophin and dystrophin in perivascular astrocytes is dependent upon the presence of α-dystrobrevin