Ganong's Review of Medical Physiology, 23rd Edition

38 SECTION I Cellular & Molecular Basis of Medical Physiology
CELL ADHESION MOLECULES
Cells are attached to the basal lamina and to each other by cell
adhesion molecules (CAMs) that are prominent parts of the
intercellular connections described below. These adhesion
proteins have attracted great attention in recent years because
of their unique structural and signaling functions found to be
important in embryonic development and formation of the
nervous system and other tissues, in holding tissues together
in adults, in inflammation and wound healing, and in the metastasis
of tumors. Many CAMs pass through the cell membrane
and are anchored to the cytoskeleton inside the cell.
Some bind to like molecules on other cells (homophilic binding),
whereas others bind to nonself molecules (heterophilic
binding). Many bind to laminins, a family of large crossshaped
molecules with multiple receptor domains in the extracellular
matrix.
Nomenclature in the CAM field is somewhat chaotic, partly
because the field is growing so rapidly and partly because of
the extensive use of acronyms, as in other areas of modern
biology. However, the CAMs can be divided into four broad
families: (1) integrins, heterodimers that bind to various
receptors; (2) adhesion molecules of the IgG superfamily of
immunoglobulins; (3) cadherins, Ca 2+ -dependent molecules
that mediate cell-to-cell adhesion by homophilic reactions;
and (4) selectins, which have lectin-like domains that bind
carbohydrates. Specific functions of some of these molecules
are addressed in later chapters.
The CAMs not only fasten cells to their neighbors, but they
also transmit signals into and out of the cell. For example,
cells that lose their contact with the extracellular matrix via
integrins have a higher rate of apoptosis than anchored cells,
and interactions between integrins and the cytoskeleton are
involved in cell movement.
INTERCELLULAR CONNECTIONS
Intercellular junctions that form between the cells in tissues
can be broadly split into two groups: junctions that fasten the
cells to one another and to surrounding tissues, and junctions
that permit transfer of ions and other molecules from one cell
to another. The types of junctions that tie cells together and
endow tissues with strength and stability include tight junctions,
which are also known as the zonula occludens (Figure
2–8). The desmosome and zonula adherens also help to hold
cells together, and the hemidesmosome and focal adhesions
attach cells to their basal laminas. The gap junction forms a
cytoplasmic “tunnel” for diffusion of small molecules (< 1000
Da) between two neighboring cells.
Tight junctions characteristically surround the apical margins
of the cells in epithelia such as the intestinal mucosa, the
walls of the renal tubules, and the choroid plexus. They are
also important to endothelial barrier function. They are
made up of ridges—half from one cell and half from the
other—which adhere so strongly at cell junctions that they
Tight
junction
(zonula
occludens)
Zonula
adherens
Desmosomes
Gap
junctions
Hemidesmosome
FIGURE 2–8 Intercellular junctions in the mucosa of the small
intestine. Tight junctions (zonula occludens), adherens junctions
(zonula adherens), desmosomes, gap junctions, and hemidesmosomes
are all shown in relative positions in a polarized epithelial cell.
almost obliterate the space between the cells. There are three
main families of transmembrane proteins that contribute to
tight junctions: occludin, junctional adhesion molecules
(JAMs), and claudins; and several more proteins that interact
from the cytosolic side. Tight junctions permit the passage
of some ions and solute in between adjacent cells
(paracellular pathway) and the degree of this “leakiness”
varies, depending in part on the protein makeup of the tight
junction. Extracellular fluxes of ions and solute across epithelia
at these junctions are a significant part of overall ion and
solute flux. In addition, tight junctions prevent the movement
of proteins in the plane of the membrane, helping to
maintain the different distribution of transporters and channels
in the apical and basolateral cell membranes that make
transport across epithelia possible.
In epithelial cells, each zonula adherens is usually a continuous
structure on the basal side of the zonula occludens, and
it is a major site of attachment for intracellular microfilaments.
It contains cadherins.
Desmosomes are patches characterized by apposed thickenings
of the membranes of two adjacent cells. Attached to the
thickened area in each cell are intermediate filaments, some
running parallel to the membrane and others radiating away
from it. Between the two membrane thickenings the intercellular
space contains filamentous material that includes cadherins
and the extracellular portions of several other transmembrane
proteins.
Hemidesmosomes look like half-desmosomes that attach
cells to the underlying basal lamina and are connected