β-dystrobrevin, a kinesin-binding receptor, interacts with the extracellular matrix components pancortins

✍ Scribed by Caterina Veroni; Margherita Grasso; Gianfranco Macchia; Carlo Ramoni; Marina Ceccarini; Tamara C. Petrucci; Pompeo Macioce

• Publisher: John Wiley and Sons
• Year: 2007
• Tongue: English
• Weight: 544 KB
• Volume: 85
• Category: Article
• ISSN: 0360-4012
• DOI: 10.1002/jnr.21186

✦ Synopsis

Abstract

The dystrobrevins (α and β) are components of the dystrophin‐associated protein complex (DPC), which links the cytoskeleton to the extracellular matrix and serves as a scaffold for signaling proteins. The precise functions of the β‐dystrobrevin isoform, which is expressed in nonmuscle tissues, have not yet been determined. To gain further insights into the role of β‐dystrobrevin in brain, we performed a yeast two‐hybrid screen and identified pancortin‐2 as a novel β‐dystrobrevin‐binding partner. Pancortins‐1–4 are neuron‐specific olfactomedin‐related glycoproteins, highly expressed during brain development and widely distributed in the mature cerebral cortex of the mouse. Pancortins are important constituents of the extracellular matrix and are thought to play an essential role in neuronal differentiation. We characterized the interaction between pancortin‐2 and β‐dystrobrevin by in vitro and in vivo association assays and mapped the binding site of pancortin‐2 on β‐dystrobrevin to amino acids 202–236 of the β‐dystrobrevin molecule. We also found that the domain of interaction for β‐dystrobrevin is contained in the B part of pancortin‐2, a central region that is common to all four pancortins. Our results indicate that β‐dystrobrevin could interact with all members of the pancortin family, implying that β‐dystrobrevin may be involved in brain development. We suggest that dystrobrevin, a motor protein receptor that binds kinesin heavy chain, might play a role in intracellular transport of pancortin to specific sites in the cell. © 2007 Wiley‐Liss, Inc.