Biology Reference
In-Depth Information
adhesion between cells; cells of one type aggregate together and sort-out from
other cells (Steinberg, 1964; Takeichi, 1991). For the purpose of this review,
we will focus on our recent studies to examine cell-cell interactions in
mammalian simple epithelia and the question of how cell change from a
migratory phenotype to a non-migratory, cell-cell adhesion phenotype. Much
of our insight into mechanism has come from the study of live cells, and some
of the phenomena were first observed over 30 years ago by Professor Michael
Abercrombie including the formation of ruing membranes and the dynamics
of lamellipodia (Abercrombie et al., 1970a,b).
Studies to understand the basis of cell-cell adhesion were underway at the
turn of the 19th century and had a mechanical focus in which movements and
forces underlying the properties of cell-cell interactions were measured
(Trinkaus, 1965). When molecules involved in cell-cell adhesion were
discovered in the 1980s (Steinberg, 1964; Gumbiner, 1996; Jamora and
Fuchs, 2002), the focus shifted to understanding the molecular and
biochemical nature of protein-protein interactions and assembly of protein
complexes. A goal of the current work is to combine our new understanding of
these protein complexes with the mechanics of cell-cell adhesion (Adams and
Nelson, 1998).
Epithelial cell-cell adhesion complexes
While many cell types require cell-cell adhesion for function, it is in simple
epithelial cells that the complexity of structural and functional organization is
greatest. In addition to distinctive organizations of membrane proteins,
cytoskeleton and organelles, simple epithelial cells have a higher-ordered
organization involving cell-cell and cell-extracellular matrix contacts that
orientates cells into a monolayer that separates different biological compart-
ments in the body (Rodriguez-Boulan and Nelson, 1989). The cell surface
bounded by these contacts (basal-lateral membrane) and facing the inside
(serosa) of the organism is structurally and functionally distinct from the
unbounded surface (apical membrane) facing a free space (lumen) that is
usually continuous with the outside of the organism. Functional differences
between these plasma membrane domains are required to regulate vectorial
transport of ions and solutes across the epithelium, and abnormalities in
epithelial organization, cell-cell adhesion and protein distributions are
characteristic of many diseases (Rodriguez-Boulan and Nelson, 1989).
Understanding how different membrane domains are organized in polarized
epithelial cells requires knowledge of how cells adhere to each other and the
extracellular matrix, and how the resulting bounded and unbounded cell
surfaces are converted into different membrane domains by localized assembly
and targeted delivery of specific proteins (Yeaman et al., 1999).
