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Dystrophin-associated protein scaffolding in brain requires -dystrobrevin

Bragg, April D.; Das, Sonal S.; Froehner, Stanley C.

doi: 10.1097/WNR.0b013e32833b0a3b
Cellular, Molecular and Developmental Neuroscience

Dystrophin and the α-dystrobrevins bind directly to the adapter protein syntrophin to form membrane-associated scaffolds. At the blood–brain barrier, α-syntrophin colocalizes with dystrophin and the α-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 γ2-syntrophin, α-dystrobrevin-2, and dystrophin to glial endfeet is also dependent on the presence of α-syntrophin. In this 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 in which assembly of an astroglial protein scaffold containing syntrophin and dystrophin in perivascular astrocytes is dependent on the presence of α-dystrobrevin.

Department of Physiology and Biophysics, University of Washington, Seattle, Washington, USA

Correspondence to Stanley C. Froehner, PhD, Department of Physiology and Biophysics, HSB Room G424, PO Box 357290, University of Washington, 1705 NE Pacific St, Seattle, WA 98195, USA

Tel: +1 206 543 0950; fax: +1 206 685 0619; e-mail: froehner@uw.edu

Present address: April D. Bragg, Centerstone Research Institute, 44 Vantage Way, Suite 280, Nashville, TN 37228, USA; Sonal S. Das, The Michael J. Fox Foundation for Parkinson's Research, Church Street Station, PO Box 780, New York, NY 10008-0780, USA

Received 13 April 2010 accepted 15 April 2010

© 2010 Lippincott Williams & Wilkins, Inc.