Dermal microvascular endothelial cells play important roles in cutaneous biology, during both normal and pathological settings. An important function of endothelial cells is to provide a selective barrier between the plasma and tissue compartments that regulates the flux of fluid and plasma derived cells into the tissue extracellular space. The loss of endothelial barrier function is associated with inflammation and edema in a number of cutaneous diseases. Adhesive intercellular junctions that form between adjacent endothelial cells are thought to play crucial roles in endothelial barrier function. VE-cadherin is the major adhesion molecule that resides at endothelial cell junctions and plays an important role in endothelial barrier function. In addition, VE-cadherin function is required for the formation of tubules during neovascularization, a process that is important during development, wound healing, and tumorigenesis. VE- cadherin interactions with the cytoskeleton are thought to be fundamental to VE-cadherin function in endothelial cells. Plakoglobin and beta-catenin are part of the armadillo (arm) family of proteins and play important roles in attaching cadherins to the cytoskeleton. A newly described protein, termed p0071 (p71) is also a member of the arm family and is expressed in endothelial cells where it co-localizes at endothelial intercellular junctions with VE-cadherin. The purpose of this application is to 1) characterize the distribution of p71 in endothelial cells both morphologically and biochemically 2) analyze the binding partners for p71 in endothelial junctions and 3) begin a functional analysis of p71 in dermal microvascular endothelial cell behavior. These studies are designed to provide the basis for an individual research proposal focusing on the role of this novel arm protein in dermal microvascular endothelial barrier function and neovascularization.
| Calkins, Catharine C; Hoepner, Bridgett L; Law, Christine M et al. (2003) The Armadillo family protein p0071 is a VE-cadherin- and desmoplakin-binding protein. J Biol Chem 278:1774-83 |
