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The Interaction with HMG20a/b Proteins Suggests a Potential Role for β-Dystrobrevin in Neuronal Differentiation*

By Benedetta Artegiani, Catherine Labbaye, Antonella Sferra, Maria Teresa Quaranta, Paola Torreri, Gianfranco Macchia, Marina Ceccarini, Tamara C. Petrucci and Pompeo Macioce

Abstract

α and β dystrobrevins are cytoplasmic components of the dystrophin-associated protein complex that are thought to play a role as scaffold proteins in signal transduction and intracellular transport. In the search of new insights into the functions of β-dystrobrevin, the isoform restricted to non-muscle tissues, we performed a two-hybrid screen of a mouse cDNA library to look for interacting proteins. Among the positive clones, one encodes iBRAF/HMG20a, a high mobility group (HMG)-domain protein that activates REST (RE-1 silencing transcription factor)-responsive genes, playing a key role in the initiation of neuronal differentiation. We characterized the β-dystrobrevin-iBRAF interaction by in vitro and in vivo association assays, localized the binding region of one protein to the other, and assessed the kinetics of the interaction as one of high affinity. We also found that β-dystrobrevin directly binds to BRAF35/HMG20b, a close homologue of iBRAF and a member of a co-repressor complex required for the repression of neural specific genes in neuronal progenitors. In vitro assays indicated that β-dystrobrevin binds to RE-1 and represses the promoter activity of synapsin I, a REST-responsive gene that is a marker for neuronal differentiation. Altogether, our data demonstrate a direct interaction of β-dystrobrevin with the HMG20 proteins iBRAF and BRAF35 and suggest that β-dystrobrevin may be involved in regulating chromatin dynamics, possibly playing a role in neuronal differentiation

Topics: Neurobiology
Publisher: American Society for Biochemistry and Molecular Biology
OAI identifier: oai:pubmedcentral.nih.gov:2915710
Provided by: PubMed Central
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