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

1072 Chapter 19: Cell Junctions and the Extracellular Matrix
muscle cell
cut so that it
degenerates
nerve cut
shell of
residual
basal lamina
neuromuscular
junction
DEGENERATED MUSCLE AND NERVE
junctional
basal lamina
REGENERATED
NERVE FIBER
REGENERATED
MUSCLE FIBER
regenerated nerve
returns to site of
original junction
new acetylcholine
receptors become
concentrated at
site of original
junction
with special isoforms of type IV collagen and laminin and a proteoglycan called
agrin. After a nerve or muscle injury, the basal lamina at the synapse has a central
role in reconstructing the synapse at the correct location (Figure 19–54). Defects
in components of the basal lamina at the synapse are responsible for some forms
of muscular dystrophy, MBoC6 m19.44/19.55
in which muscles develop normally but then degenerate
later in life.
Figure 19–54 Regeneration experiments
demonstrating the special character
of the junctional basal lamina at a
neuromuscular junction. If a frog muscle
and its motor nerve are destroyed,
the basal lamina around each muscle
cell remains intact and the sites of the
old neuromuscular junctions are still
recognizable. When the nerve, but not the
muscle, is allowed to regenerate (upper
right), the junctional basal lamina directs
the regenerating nerve to the original
synaptic site. When the muscle, but not
the nerve, is allowed to regenerate (lower
right), the junctional basal lamina causes
newly made acetylcholine receptors (blue)
to accumulate at the original synaptic site.
These experiments show that the junctional
basal lamina controls the localization of
synaptic components on both sides of the
lamina. Some of the molecules responsible
for these effects have been identified.
Motor neuron axons, for example, deposit
agrin in the junctional basal lamina, where
it regulates the assembly of acetylcholine
receptors and other proteins in the
junctional plasma membrane of the muscle
cell. Reciprocally, muscle cells deposit a
particular isoform of laminin in the junctional
basal lamina, and this molecule is likely to
interact with specific ion channels on the
presynaptic membrane of the neuron.
Cells Have to Be Able to Degrade Matrix, as Well as Make It
The ability of cells to degrade and destroy extracellular matrix is as important as
their ability to make it and bind to it. Rapid matrix degradation is required in processes
such as tissue repair, and even in the seemingly static extracellular matrix
of adult animals there is a slow, continuous turnover, with matrix macromolecules
being degraded and resynthesized. This allows bone, for example, to be
remodeled so as to adapt to changes in the stresses on it.
From the point of view of individual cells, the ability to cut through matrix is
crucial in two ways: it enables them to divide while embedded in matrix, and it
enables them to travel through it. Cells in connective tissues generally need to be
able to stretch out in order to divide. If a cell lacks the enzymes needed to degrade
the surrounding matrix, it is strongly inhibited from dividing, as well as being hindered
from migrating.
Localized degradation of matrix components is also required wherever cells
have to escape from confinement by a basal lamina. It is needed during normal
branching growth of epithelial structures such as glands, for example, to allow the
population of epithelial cells to increase, and needed also when white blood cells
migrate across the basal lamina of a blood vessel into tissues in response to infection
or injury. Matrix degradation is important both for the spread of cancer cells
through the body and for their ability to proliferate in the tissues that they invade
(discussed in Chapter 20).
In general, matrix components are degraded by extracellular proteolytic
enzymes (proteases) that act close to the cells that produce them. Many of these
proteases belong to one of two general classes. The largest group, with about 50
members in vertebrates, is the matrix metalloproteases, which depend on bound
Ca 2+ or Zn 2+ for activity. The second group is the serine proteases, which have a
highly reactive serine in their active site. Together, metalloproteases and serine