Chemistry Reference
In-Depth Information
sterically inhibiting cell-cell apposition during neuronal differentiation. PSA-
NCAM has an important role in regeneration of axons and dendrites, thereby
accounting for its upregulation after a lesion. Immature synapses express more
PSA-NCAM than mature ones, suggesting a role in learning and memory. L1 is
another member of the immunoglobulin superfamily, structurally similar to
NCAM but lacking PSA (Figure 30.4). A donor of high oligomannosidic glycans,
L1 can associate with NCAM, an oligomannoside receptor, and disruption of this
interaction interferes with neurite outgrowth [22]. Mutations in the gene for L1
lead to human genetic diseases including mental retardation.
The HNK-1 glycan, so named as the epitope recognized by the monoclonal
antibody that binds to human natural killer cells, consists of 3
- sulfated glucuronic
acid attached to lactosamine (for structure, please see Chapter 1 and Figure 1.7 c).
It is present on
N
- and
O
-glycans associated with a large variety of recognition
molecules, including NCAM, L1, chondroitin sulfate proteoglycans ( CSPGs ), inte-
grins, tenascin and various myelin glycoproteins (see below) [22] . Receptors that
bind HNK-1 have been identifi ed, such as the extracellular matrix ( ECM ) glyco-
proteins laminin and merosin and the cell-surface lectins L- and P-selectins (for
further information on selectins, please see Chapters 19 and 27.3 and Figure 29.5;
for an X-ray structure of P-selectin, see Figure 16.1h). Interestingly, in myelinating
mice, HNK-1 is expressed selectively by Schwann cells associated with motor
axons, but not by those associated with sensory axons. HNK-1 also occurs on gly-
colipids in Schwann cells which show similar preferential expression on motor
nerves [22] .
Oligomannosidic glycans as components of neural recognition glycoproteins are
uniquely abundant in the nervous system. These glycans contain variable numbers
of
′
-mannosyl residues attached to the peptide backbone via the GlcNAc
core [22]. They are normally transient structures that appear on glycoproteins
during biosynthesis, further processing of the oligosaccharide in the Golgi appa-
ratus having been blocked where they persist. In brain, as opposed to most other
tissues, oligomannosides are carried to the cell surface as part of such molecules
as L1. Oligomannosidic glycans are particularly abundant in the rodent brain and
in the adult are concentrated in synapses. Glutamatergic synapses also contain
lectins that bind to these glycans. An adhesion molecule on glia known as AMOG,
which is also the
α
- and
β
β
- subunit of Na
+
/K
+
-ATPase, contains 80% of its glycans as
oligomannosides.
The role of recognition glycoproteins in neurite outgrowth includes both inhibi-
tory and conducive reactions. Tenascins are ECM glycoproteins that interact with
such proteoglycans as heparin and heparan sulfate (please see Chapter 11 for
information on these proteoglycans). Tenascin- C and - R promote neuron migra-
tion or neurite extension when uniformly distributed as substrate in brain or the
PNS, but inhibit such activities when expressed at discontinuous boundaries. They
are highly enriched at nodes of Ranvier of both CNS and PNS axons. The specifi c
molecular domains in tenascin-C and -R that are conducive and inhibitory have
been structurally identifi ed [23]. Semaphorins and ephrins also regulate axonal
guidance in the developing nervous system through a combination of attractive
and repulsive signals. Finally, proteoglycans, often in conjunction with recognition
