Integrins and cadherins are important cellular sensors driving key developmental and physiological processes. The development and maintenance of tissues relies on multiple signals, including those transmitted by non-diffusing molecules expressed on the surface of cells, or secreted into the extracellular matrix. An example of the first class are cadherins, transmembrane receptors that mediate homophilic binding with homologous proteins in adjacent cells. Cadherins represent an important family of cell-cell adhesion receptors. Signals from extracellular matrix molecules are transduced into cells through another important family of transmembrane receptors: integrins. Integrins mediate adhesion of cells to a variety of extracellular matrix proteins. Assembly/disassembly of cadherin and integrin adhesion complexes occur many times during development, leading to rearrangements of cellular layers, cell disociation and cell migration, and formation of tissues. One of the great challenges for the next future is to define the full range of interactions and regulatory mechanisms associated with functional cell adhesion receptors. In a broad sense, our laboratory study the regulation of integrin function, and the impact of this regulation on cellular behavior.
Specifically, our laboratory focuses on the regulation of cadherin and integrin-mediated adhesion by Protein Tyrosine Phosphatase 1B (PTP1B). PTP1B anchors to the cytosolic face of the ER by a short C-terminus sequence. In addition to this location, we have found that PTP1B is a constituent of the integfin and cadherin adhesion complexes. We try to address: 1) the molecular determinants that target PTP 1B to the cell adhesion complexes and 2) the molecular pathways regulated by PTP1B in the cell adhesion complexes and its role in cell motility and differentiation. On the integrin side, we have evidence showing that PTP 1B is positioned over cell-matrix sites by dynamic extensions of the ER, event that depends on microtubules. We have recently shown that PTP1B promotes the association of p120 catenin to the N-cadherin precursor, facilitating the trafficking of the complex from the ER to the Golgi complex.