Dave Roberts       2005-Present   
Postdoctoral Fellow
Ph.D. University of North Carolina
Funded by Lineberger Cancer Center
A model system to study the tumor suppressor APC and its role in Wnt regulation
Cadherin-catenin complexes, localized to adherens junctions, are essential for cell-cell adhesion. One means of regulating adhesion is through the juxtamembrane domain of the cadherin cytoplasmic tail. This region is the binding site for p120, leading to the hypothesis that p120 is a key regulator of cell adhesion. p120 has also been suggested to regulate the GTPase Rho, and to regulate transcription via its binding partner Kaiso. To test these hypothesized functions, we turned to Drosophila. Drosophila has only a single p120 family member, which localizes to adherens junctions and binds the juxtamembrane region of DE-Cadherin. We generated null alleles of p120, and found that mutants are viable and fertile and have no apparent changes in junction structure or function. However, p120 mutations strongly enhance mutations in the genes encoding DE-Cadherin or Armadillo, the ß-catenin homolog.
Finally, we examined the localization of p120 during embryogenesis. p120 localizes to adherens junctions, but its localization there is less universal than that of core adherens junction proteins. Together, these data suggest that p120 is an important positive modulator of adhesion, but that it is not an essential core component of adherens junctions. We are now interested in determining the mechanism by which p120 regulates adhesion, and examining whether it it plays an independent role in regulating the small GTPases of the Rho family.

Publications
Roberts, D.M, Anderson, A.L, Hidaka, M, Swetenburg, R.L, Patterson, C, Stanford, W.L, Bautch, V.L.
(2004) A vascular gene trap screen defines RasGRP3 as an angiogenesis-regulated gene required for the endothelial response to phorbol esters. Mol Cell Biol. 24:10515-28.

Roberts, D.M, Kearney, J.B, Johnson, J.H, Rosenberg, M.P, Kumar, R, Bautch, V.L. (2004)
The vascular endothelial growth factor (VEGF) receptor Flt-1 (VEGFR-1) modulates Flk-1 (VEGFR-2) signaling during blood vessel formation. Am J Pathol. 164:1531-5.