Chemistry Reference
In-Depth Information
jugates revealed neuroligin to be localized in the postsynaptic membrane, whereas
neurexin 1
is largely confi ned to the presynaptic membrane [25]. Both of these
are type I membrane proteins with a glycosylated extracellular sequence, a single
transmembrane region and a relatively short intracellular segment. Signifi cantly,
they bind to each other only in the presence of Ca
2+
, which is known to occur in
the synaptic gap. Proteoglycans also occur prominently at the synapse and neuro-
muscular junction (see below).
β
30.9
Glycoproteins of Myelin
Myelin is formed as a spiraling, multilamellar, lipid-rich extension of the plasma
membrane of Schwann cells in the PNS and oligodendrocytes in the CNS. It serves
to insulate the axon and promote rapid saltatory conduction. As with the ganglio-
sides, glycoproteins of CNS and PNS myelin differ signifi cantly [26] . Glycoproteins
comprise a majority of total protein in PNS myelin, but a rather small minority in
CNS myelin. Po is a 30-kDa type 1 transmembrane glycoprotein that comprises
over half the total protein in compact PNS myelin. It contains a single extracellular
Ig-like domain and one
N
-linked oligosaccharide that is very heterogeneous; many
of these are terminated in sialic acid and sulfated glucuronic acid, the latter com-
prising the HNK-1 epitope. Po is viewed as stabilizing the compact lamellar
structure through homophilic interactions that may occur in both
cis
- and
trans
-
modes. The other glycoprotein of PNS myelin is PMP- 22, a 22 - kDa protein that
accounts for less than 5% and appears to be a tetraspanin protein with a glycosyl-
ation pattern similar to that of Po. The fi rst glycoprotein to be identifi ed in CNS
myelin was MAG (see above), a 100-kDa molecule that contains about 30% by
weight carbohydrate [26]. The oligosaccharides are heterogeneous and negatively
charged due to sialic acid and/or sulfate, the latter refl ecting HNK-1. It has
fi ve extracellular Ig-like domains (it is an I-type lectin of the siglec group, that is
siglec-4; please see Table 27.6, Chapter 19 and below for further information), a
single transmembrane region and a cytoplasmic domain that occurs in two devel-
opmentally regulated forms. It is a minor component of both CNS and PNS
myelin, localized mainly in the periaxonal and other specialized glial membranes;
this contrasts with the major CNS myelin proteins (proteolipid protein, myelin
basic protein) which are not glycosylated and occur in compacted myelin. Studies
with MAG null mice indicated MAG is not essential for myelination, although
such mice exhibited subtle structural abnormalities in the periaxonal region of
CNS myelin sheaths. MAG is now seen as a bifunctional protein, able to stimulate
axon regrowth from young neurons while inhibiting regrowth of adult axons after
injury (see below). Myelin oligodendrocyte glycoprotein (MOG) is localized on the
outer surface of CNS myelin sheaths and oligodendrocytes. Like MAG, it is a
member of the Ig superfamily but with a single Ig-like variable domain. It contains
one site for
N
-linked glycosylation and two hydrophobic, potential transmembrane
domains. It is highly immunogenic and its possible implication in multiple
