Chemistry Reference
In-Depth Information
Info Box 2
One reason to use model organisms is to perform otherwise diffi cult experi-
ments and then draw conclusions as to the human situation (see also Chapter
23). However, ablation of genes that encode proteins with the same biochemical
activity can have widely different effects. Taking the example of GnT-I (the fi rst
GnT necessary for the generation of complex
N
- glycans; see Table 8.1), a knock-
out worm in the lab is still alive, whereas a deletion in this gene in mice is
embryonic lethal. Indeed, during evolution, it would appear that the ability of
organisms to modify their
N
- glycans by GnT -I has become associated with
more and more important processes; on the other hand, even if they display
no obvious developmental defects, a plant or a worm lacking GnT-I may not
really have a chance in the 'wild' either.
serine or threonine) are much more complex than those in the fruit fl y and carry
fucose, glucose and galactose residues; the presence of cytosolic
O
- GlcNAc is
involved in various signalling events, including a insulin-like pathway, but (unlike
in mammals) is not essential under laboratory conditions. The correct formation
of glycosaminoglycans, though, is essential for normal worm development as
exemplifi ed by the series of eight
sqv
(squashed vulva) mutants, each of which
possesses a different defect in chondroitin biosynthesis [23]; mutations in
O
-fucosylation also affect development. Finally, the glycosphingolipids of
C. elegans
are of interest since some of these, as in other nematodes, carry phosphorylcho-
line; other worm glycosphingolipids act as receptors for one of the
Bacillus thurin-
giensis
crystal toxins (some of which are used as biological pesticides) and a series
of defects in worm glycolipid biosynthesis result in the so-called
bre
(
Bacillus
resistance) mutants [24] .
8.6
Protozoan Glycosylation
As with 'worms', many protozoans (unicellular organisms) are also parasites;
examples include the trypanosomatids (for example
Trypanosoma brucei,
which
causes sleeping sickness), the malaria parasite
Plasmodium falciparum
, the dysen-
tery amoeba
Entamoeba histolytica
and the opportunistic pathogen
Acanthamoeba
castellanii
(which causes a corneal keratitis in some contact lens wearers and an
encephalitis in some immunodefi cient patients). Protozoans express a lot of pro-
teins anchored via GPI anchors and indeed this type of modifi cation was fi rst
intensely studied in
T. brucei
(particularly in the context of the anchor of the variant
surface glycoproteins of this species; see also Chapter 9). Some species also express
forms of GPI anchors that are not linked to proteins, such as the glycoinositol-
