Chemistry Reference
In-Depth Information
6
N
- Glycosylation
Christian Zuber and J ΓΌ rgen Roth
Previous chapters have described the structural and chemical aspects of glycans.
In this chapter, I will be your guide for a journey along the secretory pathway to
give you some ideas on how
N
-glycans are synthesized and infl uence my destiny
and function. So let me introduce myself. Some people consider me as a develop-
mentally cell type- and growth state-dependent regulated DNA sequence that gives
rise to differently spliced mRNAs. Others view me as a developmentally regulated
protein with a versatile set of outfi ts. You can call me just neural cell adhesion
molecule 1 (NCAM1). The ride we will take stands as a model for the route that
(glyco)proteins take along the secretory pathway. Although the events occurring
during this journey are based on solid experimental evidence, their exact role in
the biosynthesis of my
N
-glycans has not been fully elucidated. All human enzymes
involved in my maturation process will be named according to the Swiss-Prot
database (www.expasy.org; www.uniprot.org) with their entry names (primary
protein accession number).
6.1
NCAM1
NCAM1 [NCA1 (P13591; P13592)], one of the most thoroughly studied molecules
in the nervous system, is coded by a single copy gene that can give rise up to 30
distinct isoforms (Figure 6.1; for further details on NCAM1, please see Chapter
30.7). As a member of the immunoglobulin superfamily of adhesion molecules,
I have fi ve immunoglobulin-like C2-type domains, which are formed by intramo-
lecular disulfi de bonds.
All NCAM1 isoforms, as proteins destined for the extracellular space, are tar-
geted by a N-terminal hydrophobic signal peptide so that they can be translated
via the sec61 pore across the rough endoplasmic reticulum ( ER ) membrane into
the secretory pathway [1]. The ER lumen, the fi rst luminal cellular compartment
I encounter, provides an ideal physicochemical environment for proper folding
into a native protein conformation (see below). Nascent NCAM1 polypeptide
