Rho-GTPases and Muscle Differentiation: Spatio-Temporal Control of Rac1-Activity and Specific Signaling Pathways

• Applicant: Dr. Thomas Samson
• Subject Area: Cell Biology
• Term: from 2005 to 2008
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 14598342

Rho-GTPases are signaling molecules, which can cycle between active and inactive conformations and are involved in the regulation of versatile cellular functions. Especially the Rho-GTPase Rac1 is known for its ability to influence different steps of the differentiation of muscle precursor cells (myoblasts) to mature muscles. In myoblasts the total Rac1 activity decreases at the beginning of differentiation. However, locally restricted activation of this Rho-GTPase at certain areas in the differentiating cell seems to be essential, as for instance at sites of membrane fusion. Only recently, experimental methods have become available, which allow to depict local activation of Rho-GTPases in living cells. Such techniques are based upon a process, which is known as `fluorescenceresonance- energy-transfer¿ (FRET). This project aims to study the spatio-temporal distribution of Rac1 activation during myoblast differentiation by employing these novel technologies. In parallel, the role of Def- 6 during myogenesis will be analysed, as Def-6 is a Rac1 activating guanine-nucleotideexchange- factor (GEF). Interestingly, previous experiments showed that Def-6 interacts with the intracellular domain of the ¿7A integrin chain, which is expressed in differentiating myoblasts. It is presumed that Def-6-GEF-activity is regulated by this interaction in a muscle specific way. Thus, this project also aims to study the influence of Def-6 on local Rac1-activation in differentiating myoblasts and to the regulation of Def-6-GEF-activity by its binding to the ¿7A chain.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Keith Burridge