Healthcare and Medicine Reference
In-Depth Information
THE STICKY SYNAPSE
A
Myoball
Neuron
Growth cone
Adhesion between growth cones and target cells
increases rapidly upon contact (Evers et al., 1989). To
demonstrate this sort of adhesion in vitro, round
muscle cells, known as myoballs, were lifted off the
culture dish with an electrode and placed in contact
with the growing tip of a Xenopus spinal neuron
(Figure 8.10). At either 1.5 or 15 minutes after a contact
was initiated, the intercellular adhesion was catego-
rized by observing how much the neurite was
deformed by the retracted myoball. A low level of
adhesion is evident after 1.5 minutes, and the percent-
age of tightly adherent contacts more than doubles
during the first 15 minutes of contact.
What kinds of adhesion molecules are involved in
the formation of early contacts? At the nerve-muscle
junction, NCAM is gradually lost during innervation
but reappears at the endplate following denervation.
This suggests that NCAM facilitates synapse forma-
tion, but nerve-muscle contacts appear to develop nor-
mally in NCAM knockout mice (Covault and Sanes,
1985; Moscoso et al., 1998). The initial development of
motor synapses in fruit flies is also normal in the
absence of FasII, a homolog of NCAM (Schuster et al.,
1996a). However, the synapses retract from the muscle
in slightly older animals, suggesting that this cell
adhesion molecule is required for the stabilization of
connections. A second set of adhesion molecules that
could facilitate synapse differentiation are found in the
extracellular matrix (see Chapter 5). Muscle cells syn-
thesize and deposit the ECM molecule, s-laminin, in
the synaptic cleft, which can inhibit neurite outgrowth.
This growth-inhibiting activity may promote the trans-
formation of a growth cone into a presynaptic termi-
nal (Porter et al., 1995). In s-laminin knockout mice,
there is dramatic decrease of vesicle-associated phos-
phoproteins, called synapsins , in presynaptic motor ter-
minals (Noakes et al., 1995).
Several groups of cell adhesion molecules are local-
ized at developing synapses, and many of these contain
immunoglubin-domains. For example, synCAM is a
brain-specific adhesion molecule that was discovered
by searching for a mammalian homolog of FasII, the
Drosophila cell adhesion molecule that contributes to
nerve-muscle synaptogenesis. SynCAM expression
gradually increases in rat brain during the first three
postnatal weeks and is highly enriched at both pre- and
postsynaptic plasma membrane. When nonneuronal
cells are transfected with SynCAM, they can induce
presynaptic differentiation in cultured hippocampal
neurons, and these terminals are able to release gluta-
mate (Biederer et al., 2002).
Contact
Grade of
adhesion
0
1
2
3
B
15
1.5 min contact
15 min contact
10
5
0
1
2
3
Grade of Adhesion
FIGURE 8.10 Rapid adhesion between growth cone and post-
synatpic muscle cell. A. A muscle cell was manipulated into contact
with a growth cone in a dissociated cultures of Xenopus spinal cord.
After 1.5 or 15 minutes, the muscle cell was withdrawn, and the
degree of adhesion was graded: (0) no attachment, (1) filamentous
attachment, (2) deformation of growth cone, and (3) detachment of
growth cone from substrate. B. After 1.5 minutes of contact, most
pairs exhibited only grade 0-1 adhesion. However, after 15 minutes
of contact, the level of adhesion shifted to grade 1-3. (Adapted from
Evers et al., 1989)
A family of calcium-dependent cell adhesion mole-
cules, called cadherins, are located at many different
central synapses, including the cerebellum and hip-
pocampus. Cadherins interact with actin filaments via
catenins. In the hippocampus, two members of the
family, N-cadherin and E-cadherin, are restricted to
separate synapses along the dendrite, suggesting a role
in specific innervation patterns (Fannon and Colman,
1996).
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