Location, Location, Cis-mutation

✍ Scribed by Nadav Ahituv

• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 85 KB
• Volume: 32
• Category: Article
• ISSN: 1059-7794
• DOI: 10.1002/humu.21638

✦ Synopsis

report novel insights into the disease mechanisms linking together the co-chaperone BAG3 with dilated cardiomyopathy (DCM), a frequently fatal heart disease ultimately requiring heart transplantation. BAG3 is incorporated into mature cardiac myocytes within the sarcomeric Z-disk and is thought to fulfill co-chaperone functions by regulating HSP70. The Z-disk is a densely packed protein lattice that structurally integrates thin filaments from opposite sarcomeres cross-linked by alpha-actinin and a multitude of regulatory proteins (such as BAG3). Because of these features, Z-disks are perfectly positioned to sense sarcomeric strain and to generate trophic signals inside myocytes.

Consistent with the concept that Z-disks act as biomechanically active signalosomes, an increasing number of mutations associated with heart diseases have been identified among its components. Recent studies identified BAG3 mutations in DCM (Norton et al.,