Dr. Pierre D. McCrea
The University of Texas MD Anderson Cancer Center
Department of Genetics
Using primary neurons from rodents, mammalian cell lines and developing frog embryos, we seek to understand the essential contributions of catenin proteins. Catenins are multi-functional. For example, beta-catenin is a potent signal transducer during development and in cancer, entering the nucleus to regulate genes in varied tissues (canonical-Wnt pathway). Outside the nucleus on the other hand, catenins bind and regulate cell-cell adhesion proteins and cytoskeletal networks. Thus, catenins have roles in determining cell/ tissue shape, as well as gene activity, with more roles yet to be discovered.
We address how catenins contribute to developmental and cellular functions, for example:
1) How is the shape/ “arborization” of neuronal dendrites modulated by delta-catenin?
2) What are the distinct versus the shared functions of catenins? Are these functions coordinated?
Over the years, our trainees have uncovered a spectrum of novel complexes and functions of delta-catenin, plakophilin3-catenin, ARVCF-catenin, p120-catenin and beta-catenin. Our current work focuses upon a phospho-switch we discovered in delta-catenin that determines its’ binding to either of two novel scaffolding proteins in neurons. These two distinct delta complexes have different effects upon the cytoskeleton to favor dendrite elongation versus branching. We wish to understand their ability to alter dendritic-tree structure during formation of the nervous system, especially because failures in dendritic architecture result in prominent neurologic pathologies. In the longer term, we aspire to determine the extent to which the combined functions of catenins are networked to meet an array of cellular and developmental goals. By addressing these questions, we will better confront the basis of catenin contributions to development, and to cancer and CNS disease.