Cell Adhesion & Membrane Junctions

Cells within a tissue interact with each other and/or with the extracellular matrix (ECM) in a variety of ways. These interactions are formed by specialized membrane proteins, which in many cases not only mediate the physical interaction but also have signaling functions. A cell-cell adhesion site involves at least two proteins, one from each cell, but often contains many more proteins, which assemble into a membrane-associated macromolecular complex. We employ all three major electron microscopic approaches, electron crystallography, single particle electron microscopy and electron tomography, to elucidate the structural organization of simple as well as more complex cell-cell and cell-ECM adhesion sites.

The lens is a highly specialized tissue, which is designed to focus incoming light onto the retina at the back of the eye. This function requires the lens to be transparent. The lens accomplishes transparency through a number of unique adaptations. In particular, the lens fiber cells are packed very tightly into a hexagonal array, thus minimizing the intercellular spaces. Keeping the distance between cells below the wave length of light is important to avoid extensive light scattering by the intercellular spaces. A number of proteins in the fiber cell membrane assist the tight cell packing by forming physical interactions between adjacent cell membranes. These include integrins, cadherins, connexins, the lens-specific water pore aquaporin-0, and the lens-specific tetraspanin MP20. We work on many of these membrane proteins to understand the structural basis for cell adhesion.

Integrins are the major metazoan receptors for cell adhesion to extracellular matrix proteins and, in vertebrates, also play important roles in certain cell-cell adhesions. In addition to mediating cell adhesion, integrins make transmembrane connections to the cytoskeleton and activate many intracellular signaling pathways. Integrins and their ligands play key roles in development, immune responses, leukocyte traffic, hemostasis, and cancer. They are at the heart of many human diseases - genetic, autoimmune, and others - and they are receptors for many viruses and bacteria.

Aquaporin-0

Integrins