Chemistry Reference
In-Depth Information
glycoproteins, have major functional roles in developmental and repair processes
(see below). Glycoconjugates of all types fi gure prominently in neural stem cell
functioning during the earliest stages of development (see Info Box 2; for further
information on stem cell glycans as markers, please see Table 24.3 ).
Info Box 2
Growing interest is being directed to glycoconjugate composition and function
in neural stem cells (NSCs). [M. Yanagisawa, R.K. Yu. The expression and
functions of glycoconjugates in neural stem cells,
Glycobiology
2007;
17
, 57R -
74R]. They serve as excellent biomarkers due to their occurrence on the cell
surface and dramatic changes in expression pattern at various stages of differ-
entiation. They also have important functional roles in determining cell fate.
As development proceeds, NSCs give rise to neural precursor cells ( NPC s)
which in turn develop into neurons, astrocytes or oligodendrocytes. As one of
many examples, stage - specifi c embryonic antigen (SSEA)-1 is recognized by a
monoclonal antibody to the Lewis
x
structure [Gal
- ]. Ini-
tially considered a specifi c marker for NSCs/NPCs, it is now known that Lewis
x
is not restricted to these although it is still considered to represent an immature
status of cells. Carrier molecules for the SSEA-1 epitope in mouse embryonic
NPCs include CSPGs,
β
1,4(Fuc
α
1,3)GlcNAc
β
1
integrin and a glycolipid. Among the many other
glycans that could be cited, the Notch receptor containing an
O
- fucose glycan
within the EGF domains provides an example of inhibitory infl uence on cell
fate and/or maintenance of a progenitor pool; it is now seen as promoting
astrocyte development while inhibiting that of neurons and oligodendrocytes.
The above - mentioned
O
-GlcNAcylation has been described as necessary for
viability in embryonic stem cells and mouse embryogenesis (for further infor-
mation on
O
-GlcNAcylation, please see Chapter 7 ).
β
30.8
Glycoproteins of the Synapse
Carbohydrates were initially considered as only of secondary importance in under-
standing the synapse, but it has gradually become clear that glycans are integral
to the formation and functioning of these linkages that mediate communication
among the 10
11
CNS neurons with their estimated 10
14
synaptic connections [24] .
As mentioned, synapses contain a high proportion of oligomannosidic glycans and
also NCAM, with or without attached PSA. The latter has important roles in syn-
aptogenesis and synaptic plasticity, both in the brain and neuromuscular junction.
Mice lacking ST8Sia-IV (see above) were defective in both long-term potentiation
and long-term depression in the Schaffer collateral-CA1 projections of the hippo-
campus. A role for PSA in localizing trophic factors via GAGs at the synapse has
been suggested. The pre- and postsynaptic membranes of the synapse are held
together by adhesion complexes, and the search for membrane-specifi c glycocon-
