Chemistry Reference
In-Depth Information
ing for the same acceptor substrate, which in turn results in a mixture of different
N
-glycans at identical Asn sequons of a given glycoprotein. Diversity cannot be
explained solely by purposeful strategies of cells. It may also be the consequence
of stochastic events of competing enzyme reactions on suboptimal substrates and
of the premature stopping of synthesis due to accelerated intra- Golgi transport.
6.10
Conclusions
NCAM1 was your travel guide along the secretory pathway. Equipped with this
experience and knowledge, you know now that
N
-glycosylation is one of the more
important post- translational protein modifi cations. Without the spectrum of
N
-glycans, metazoan and vertebrate development would have resulted in outcomes
differing from those we see nowadays. Disulfi de bond formation, lysosomal target-
ing, assembly of heteromeric protein complexes in the secretory pathway and
neural plasticity are only some examples of
N
- glycan functions, indispensable for
the development of organisms and the maintenance of their function and archi-
tecture. Secretion is strongly dependent on different phylum- dependent
N
- glycan
tags. Monoglucosylated
N
-glycans provide an ER-retention tag, whereas the Man
8
-
A isomer confers ER export in vertebrates. Furthermore, the structural diversity
of
N
-glycans provided the basis for many coevolutionary events occurring during
the evolution to higher eukaryotes and vertebrates. In humans,
N
- glycosylation is
directly involved in the pathogenesis of several diseases such as protein-folding
diseases, congenital diseases of glycosylation and cancer. Even seemingly subtle
modifi cations can play signifi cant roles such as the core substitutions [23] . Thus,
the enormous diversity of
N
-glycans will continue to motivate continued research
in this fi eld, since detailed analyses will remain fundamental for future advances
to functionally decode the glycome.
Summary Box
The puzzle of
N
-glycosylation is starting to be resolved. The basic molecular
and evolutionary aspects of the synthetic and degradative pathways of
N
- glycans
are thus defi ned, but there is still a long way to go to understand the process
and implications in their entirety. In the future, system biology approaches
may help to fi ll the empty spaces and complement missing roads on this
map.
References
1
2
Alberts B
et al.
Molecular Biology of the
Cell
, 4th edn . Garland Science , London ,
2002 .
Helenius A , Aebi M . Roles of
N
- linked
glycans in the endoplasmic reticulum.
Ann
Rev Biochem
2004 ; 73 : 1019 - 49 .
