Chemistry Reference
In-Depth Information
Figure 30.4
Neural cell adhesion molecules
of the immunoglobulin superfamily. Glycopro-
teins of this family contain immunoglobulin-
like domains and fi bronectin type III (FNIII)
repeats. Of the proteins encoded by the
NCAM1 gene, many isoforms are produced by
splicing, but NCAM-120, -140, and -180 are the
major ones. NCAM members possess fi ve Ig-
like domains and two FNIII domains, while L1
contains six Ig-like domains and fi ve fi bronectin
type III repeats. Shown are the structures of the
three major isoforms of NCAM from mouse
brain (the glycans of NCAM exhibit structural
diversity). These each contain six
N
- glycan
chains with two PSA chains attached to the
fi fth Ig-like domain; HNK-1 is also present on
some glycans (please see Chapter 6 for more
detail on NCAM structures). L1 has many
N
-
glycosylation sites (not shown), about which
less is known; it contains HNK-1, but no PSA.
[Adapted with modifi cations from (a) [22] and
(b) C. Albach
et al.
Identifi cation of
N
- glycosyl-
ation sites of the murine neural cell adhesion
molecule NCAM by MALDI-TOF and MALDI-
FTICR mass spectrometry.
Anal Bioanal Chem
,
2004;
378
, 1129 - 1135.]
cytoplasmic unit (Figure 30.4). Two polysialyltransferases, ST8Sia-II and ST8Sia-
IV, that synthesize PSA on NCAM have been identifi ed [21]. The former is more
important during embryogenesis, while the latter has a role in those few areas of
the mature brain with ongoing neurogenesis or plasticity (for example olfactory
interneuron precursors, dentate gyrus of the hippocampus). Other regions of the
mature brain contain relatively little PSA. Surprisingly, complete genetic ablation
of NCAM resulted in a fairly mild phenotype - the brain showing normal cytoar-
chitecture and only small decrease in size. In contrast, complete ablation of PSA
produced animals with severely retarded postnatal development and early death.
From this and related fi ndings it was concluded that a major function of PSA is
to mask NCAM and thus prevent inappropriate NCAM interactions during devel-
opment. This is in accord with the prevailing model of PSA function as that of
