Molecular Biology of the Cell by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morgan, Martin Raff, Keith Roberts, Peter Walter by by Bruce Alberts, Alexander Johnson, Julian Lewis, David Morg

1056 Chapter 19: Cell Junctions and the Extracellular Matrix
N
Ig-like
domains
disulfide bond
N
fibronectin
type III domains
N
Figure 19–29 Two members of the
Ig superfamily of cell–cell adhesion
molecules. NCAM is expressed on
neurons and many other cell types, and
mediates homophilic binding. ICAM is
expressed on endothelial cells and some
other cell types and binds heterophilically
to an integrin on white blood cells. Both
NCAM and ICAM are glycoproteins, but
their attached carbohydrate chains are
not shown.
C
NCAM
CYTOSOL
10 nm
C
C
ICAM
quantity of sialic acid (with chains containing hundreds of repeating sialic acid
units). By virtue of their negative charge, the long polysialic acid chains can interfere
with cell adhesion (because like charges repel one another); thus, these forms
of NCAM can serve to inhibit adhesion, rather than cause it.
MBoC6 m19.20/19.30
A cell of a given type generally uses an assortment of different adhesion proteins
to interact with other cells, just as each cell uses an assortment of different
receptors to respond to the many soluble extracellular signal molecules in its
environment. Although cadherins and Ig superfamily members are frequently
expressed on the same cells, the adhesions mediated by cadherins are much
stronger, and they are largely responsible for holding cells together, segregating
cell collectives into discrete tissues, and maintaining tissue integrity. Molecules
such as NCAM seem to contribute more to the fine-tuning of these adhesive interactions
during development and regeneration, playing a part in various specialized
adhesive phenomena, such as that discussed for blood cells and endothelial
cells. Thus, while mutant mice that lack N-cadherin die early in development,
those that lack NCAM develop relatively normally but show some mild abnormalities
in the development of certain specific tissues, including parts of the nervous
system.
Summary
In epithelia, as well as in some other types of tissue, cells are directly attached to one
another through strong cell–cell adhesions, mediated by transmembrane proteins
called cadherins, which are anchored intracellularly to the cytoskeleton. Cadherins
generally bind to one another homophilically: the head of one cadherin molecule
binds to the head of a similar cadherin on an opposite cell. This selectivity enables
mixed populations of cells of different types to sort out from one another according
to the specific cadherins they express, and it helps to control cell rearrangements
during development.
The “classical” cadherins at adherens junctions are linked to the actin cytoskeleton
by intracellular adaptor proteins called catenins. These form an anchoring
complex on the intracellular tail of the cadherin molecule, and are involved not
only in physical anchorage but also in the detection of and response to tension and
other regulatory signals at the junction.
Tight junctions seal the gaps between cells in epithelia, creating a barrier to the
diffusion of molecules across the cell sheet and also helping to separate the populations
of proteins in the apical and basolateral plasma membrane domains of the
epithelial cell. Claudins are the major transmembrane proteins forming gap junctions.
Intracellular scaffold proteins organize the claudins and other junctional
proteins into a complex protein network that is linked to the actin cytoskeleton.