Chemistry Reference
In-Depth Information
Figure 30.5
Proposed mechanism for inhibi-
tion of axon outgrowth by glycans of myelin and
ECM. MAG expressed by oligodendrocytes con-
tains eight
N
- linked oligosaccharides (blank
circles) in its extracellular region. MAG binds
to ganglioside GT1b and GPI-linked NgR of
the axonal membrane, recruiting these into a
lipid raft microdomain. A complex is formed
with neurotrophin receptor P75
NTR
and the lat-
ter transmits an inhibitory signal by activating
small GTPase, RhoA. NgR alone also interacts
with Nogo ligand expressed in myelin. Astrocy-
tes inhibit axon outgrowth by producing CSPGs
after injury. GAG side-chains are shown.
[Adapted with revisions from (a) M. Vinson
et al.
Lipid rafts mediate the interaction be-
tween myelin-associated glycoprotein (MAG)
on myelin and MAG-receptors on neurons.
Mol
Cell Neurosci
2003;
22
, 344 - 352 and (b) [27] .]
and the cell-surface glycocalyx. Such assemblies have been described as perineu-
ronal nets, which are believed to contain a hyaluronan- lectican - tenascin - R complex
that constitutes the core assembly of the mature brain ECM; the glycoprotein
tenascin-R (see above) is proposed to function as a molecular cross-linker within
the complex. In the nervous system, as elsewhere, proteoglycans are characterized
by enormous structural diversity based on sugars/proteins and the degree of sul-
fation along the glycan chains of 50-150 disaccharide repeat units.
In relation to development, the neural ECM has essential roles in cell migration,
neurite outgrowth, synaptogenesis, and regulation of synaptic plasticity. As with
tenascins (see above), CSPGs promote neuritogenesis when present as a uniform
