Involvement of fractin in TGF-β-induced apoptosis in oligodendroglial progenitor cells

✍ Scribed by Ramona Schulz; Tanja Vogel; Tetsuo Mashima; Takashi Tsuruo; Kerstin Krieglstein

• Publisher: John Wiley and Sons
• Year: 2009
• Tongue: English
• Weight: 376 KB
• Volume: 57
• Category: Article
• ISSN: 0894-1491
• DOI: 10.1002/glia.20875

✦ Synopsis

Abstract

Transforming growth factor‐β (TGF‐β) induces apoptotic cell death during the development of the nervous system. We recently identified that TGF‐β induced apoptosis in oligodendroglial progenitor cells (primary cells as well as oligodendroglial cell line OLI‐neu) is characterized by down‐regulation of Bcl‐xl. In this report, we now focused on mechanisms that mediate TGF‐β dependent Bcl‐xl down‐regulation in oligodendroglial cells. We showed that the caspase‐specific cleavage product Fractin is produced in oligodendroglial cells during TGF‐β‐mediated apoptosis, which represents an early event of the cascade. Cleavage of actin into Fractin was dependent on functional actin and caspases, and occurred simultaneously with a Fractin‐Bcl‐xl‐interaction. This Fractin‐Bcl‐xl interaction indicated a connection between Bcl‐xl down‐regulation and Fractin appearance, since Bcl‐xl regulation was also dependent on caspases and functional actin, and an overexpression of Fractin induced a Bcl‐xl protein down‐regulation. Further analysis of Fractin‐Bcl‐xl interaction in other culture systems confirmed these data. In conclusion, we show that Fractin is not only an apoptotic marker, but has indeed a functional role in apoptotic signaling in oligodendrocytes. © 2009 Wiley‐Liss, Inc.