The Regulational Mechanism for the Formation of Cadherin-Catenin Complex in alpha-Catenin Level

1998 Fiscal Year Final Research Report Summary

• Project/Area Number: 09670136
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Kagoshima University
• Principal Investigator: OBAMA Hiroya Faculty of Medicine Kagoshima University, Research Associate, 医学部, 助手 (70264405)
• Project Period (FY): 1997 – 1998
• Keywords: cadherin / alpha-catenin / beta-catenin / plakoglobin / actin / phosphatidyl-inositol 4,5-bisphosphate

Research Abstract

alpha-Catenin is an important molecule for the adhesive function of cadherins, which mainly function at adherence junction through the homophilic mechanism. We have reported that alpha-catenin binds with beta-catenin or plakoglobin by its the amino-terminal region. In this study we examined firstly whether alpha-catenin can directly bind to the cytoskeleton, actin filament. Various regions of alpha-catenin were expressed as the fusion protein with glutathione-S-transferase (GST). GST/alpha-catenin fusion proteins were incubated with actin filaments. The binding ability of GST/alpha-catenin fusion proteins to actin filament was assessed by co-sedimentation assay. The assay revealed that the carboxyl-terminal region bound most strongly to actin filament. This carboxyl-terminal region was also found to be able to interact with the central region of alpha-catenin. As the affinity of alpha-catenin for the cytoskeleton is weaker than that of the carboxyl-terminal region of alpha-catenin, the interaction between central and carboxyl regions might interfere the access of the carboxyl-terminal region to actin filament. Phosphatidyl-inositol 4,5-bisphosphate (PIP2) is known to regulate functions of many actin binding proteins, for example, alpha-actinin, vinculin, gelsolin and profilin. As the next project, we checked the interaction between PIP2 and alpha-catenin. The binding assay revealed that alpha-catenin bound most strongly to PIP2 in tested five lipids, and that the carboxyl-terminal region was important for this interaction. The binding ability of alpha-catenin to actin filament might be modulated by PlP2 associated with conformational change of alpha-catenin. These results mentioned above suggest that the carboxyl-terminal region of alpha-catenin may have multi-function, actin-binding, PIP2-binding and inter-domains interaction. These functions possibly regulate the link between cadherin molecules and cytoskeleton.