Overview
What holds our cells together and keeps us from falling apart? The secret lies with specialized proteins that stick out of the cell membrane and bind specifically to other proteins in the vicinity of the cell. The “other proteins” may be embedded in a matrix (cell-matrix adhesion) or protrude from the surface of a neighboring cell (cell-cell adhesion).
Adhesion receptors must be anchored from inside so they are not pulled out of the membrane. Such anchoring is achieved by connecting the receptors to the cell’s skeleton (=cytoskeleton). The cytoskeleton, which is made of long filaments of protein, is constantly in flux and has the ability to contract and exert force. The dynamics and forces of the cytoskeleton are what allows cells to change shape and move. Cell-cell adhesions are crucial in transforming individual cell movements into coordinated tissue shape changes. Such processes are essential for embryonic development and wound healing, and their misregulation is responsible for the spreading of cancer.
Surprisingly, we still know very little about the connection between cell-cell adhesion receptors and the cytoskeleton. Current research is focused mainly on two adaptor proteins (a/b-catenin), although there is evidence that dozens of proteins are involved. Our goal is to expand the number of cell-cell adhesion adaptors we study and to learn sufficient information about each component to be able to build a model of the adaptor network. We are using a powerful combination of model organism genetics (of the nematode C. elegans) and mammalian cell culture techniques, including high resolution microscopy and micromanipulation.The knowledge gained by this research will deepen our understanding of the pivotal role of adaptors in cell-cell adhesion and may offer better diagnostics and/or therapy for common birth defects, wound healing and possibly treatment of some cancers.
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