Chemistry Reference
In-Depth Information
phospholipids in
T. cruzi
, which are immune activators, or the lipophosphoglycans
of
Leishmania
species [25]. With regard to
N
- glycosylation, some protozoans (even
though they are eukaryotes) do not synthesise the usual Glc
3
Man
9
GlcNAc
2
doli-
chol-linked precursor. In the case of
Giardia
, the
N
- glycans and the dolichol - linked
precursor contain apparently just two GlcNAc residues and lack all mannoses,
whereas trypanosomes do not add glucose to the precursor; this is due to a lack
of various
ALG
genes which encode the relevant glycosyltransferases [26] .
One protozoan is a very interesting model organism - the non - parasite
Dictyo-
stelium discoideum
, which is sometimes known either as a 'slime mold' or as a
' social amoeba '. In the unicellular state, it is an amoeba; however, upon starvation,
the cells aggregate together and form a fruiting body; the resulting spores can
survive until food levels are again suffi cient. A number of studies have been per-
formed on its
N
-glycosylation; recent studies in our laboratory, using modern
techniques, suggest that the most dominant glycan in laboratory axenic cultures
consists of Fuc
1
GlcNAc
4
Man
8
. The fucose is
1,3-linked to the core and constitutes
an epitope for anti-HRP. The slime mold also expresses novel
O
- glycans, including
a tetrasaccharide present on a cytosolic protein, and, like some trypanosomatids,
expresses mucins containing GlcNAc (rather than GalNAc) linked to serine/threo-
nine, as well as protein-linked phosphosugars [27] .
α
8.7
Fish Glycosylation
Once we reach fi sh in the evolutionary tree (and so the fi rst vertebrates), then
we cease to see many of the 'immunogenic' features of glycans from 'lower'
organisms. Indeed, it appears that zebrafi sh (
Danio rerio
) and medaka (
Oryzias
latipes
) have a similar
N
-glycomic potential as birds and mammals, with the pres-
ence of multiantennary complex, sialylated
N
-glycans having been proven [28] ;
the
O
-glycans and glycosphingolipids of zebrafi sh can also be sialylated [28] . Thus,
presumably the 'jump' to vertebrates was accompanied by a shift in the glycome.
One interesting marker of this shift is not in the realm of
N
- glycans, but is related
to glycosaminoglycan biosynthesis: fi sh (like mammals, but unlike invertebrates)
have two peptide
O
-xylosyltransferase genes and also express keratan sulphate,
in addition to chondroitin and heparan sulphates. It is also in relation to glycos-
aminoglycans that perhaps the most ' use ' of zebrafi sh as a glycobiological
model has been made. A number of mutants have been characterised, including
jekyll
which has a defect in cardiac valve formation due to a disruption in the
gene encoding UDP - Glc dehydrogenase - an enzyme required for production of
glycosaminoglycans [29]. In another study, use of morpholino-modifi ed oligonu-
cleotides demonstrated a role for heparan- modifying sulphotransferases in
vascular development [30]. Thus, just as in fl ies and worms, experiments in
fi sh show that heparan and/or chondroitin sulphates are important during
morphogenesis.
