DEVELOPMENTAL FUNCTIONS OF THE P120 CATENIN

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The catenin proteins are of high biological interest given that they bind the cytoplasmic domains of cadherin cell-cell adhesion proteins, forming a complex essential to the morphogenic sorting of tissues and the subsequent maintenance of tissue identities. Of additional intrigue, catenins bind receptor tyrosine kinases, various actin-associated proteins, the APC tumor suppressor (best characterized in the progression of human colon cancer), and components of signaling pathways that require their direct association with nuclear transcription factors. We have collaboratively revealed that the cadherin-catenin complex contains the p120 catenin, which bears structural homology with both beta-catenin and plakoglobin (gamma-catenin), and is a preferred substrate of src kinase and growth factor receptors. Our recent studies have examined the role of p120 in vertebrate development, and indicate that p120 function is critical for proper cell migration, likely resulting from its modulation of cadherin adhesive function. We have further shown that in contrast to beta-catenin, p120 does not engage in Wnt/ beta-catenin-directed nuclear signaling. However, since p120 was recently revealed to bind a novel transcription factor, Kaiso, of the POZ/zinc-finger family, p120 is likely to modulate distinct (non-Wnt/beta-catenin) transcriptional events in the nucleus. This proposal aims to discern the functions of Xenopus p120 (Xp120) and Xenopus Kaiso (XKaiso) in early vertebrate embryogenesis. The experimental system to be employed is the amphibious frog Xenopus, which will offer experimental advantages including the capacity to functionally evaluate Xp120 and XKaiso from both cellular and developmental perspectives. Aims Addressed: 1. What are the developmental functions of Xp120 in association with Cadherins? 2. What are the developmental functions of XKaiso, and to what extent are they modulated via Xp120?