Protein Glycosylation: Implications for In Vivo Functions and Therapeutic Applications - Advances in Biochemical Engineering Biotechnology - page 170

There have been some reports where no or only a minor role of attached
glycans was detected. For example, though the rat lutropin receptor is heavily
glycosylated, N -linked carbohydrates are not absolutely required for proper
folding into a form capable of binding hormone and signaling [108]. In rat
angiotensin II type-2 receptor, N -glycans have a minor contribution to the
ligand binding/affinity of the receptor and are not essential for targeting and
expression of the receptor at cell surface [109].
3.4
Intracellular Trafficking
Glycans are modified for direct targeting proteins to specific locations within
and outside the cell. The primary role of mannose-6-P receptor (MPR) in the
Golgi is to target more than 40 different hydrolytic enzymes to lysosomes by
interaction with terminal Man-6-P residues. Most mammalian cells contain two
distinct transmembrane glycoprotein MPRs, and both mediate transfer of new-
ly synthesized lysosomal proteins from trans-Golgi to endosomal compartment
[110]. Similar to Man-6-P modification of lysosomal enzymes, the possibility
exists that plasma membrane and secretory proteins also employ N -glycans as
sorting signals for transport. If N -linked glycans are used as sorting signals in
biosynthetic trafficking, the core residues should be considered as possible re-
cognition targets [3]. In spite of the postulate for the requirement of sorting
signals for trafficking beyond ER, this is an issue that being debated, and the
final answer is not distinct [111].It has recently been observed that glycoprotein
sorting is related to specific structures of glycans, as for example bisecting Gn
acts as a negative sorting signal for cell surface glycoproteins [112].
3.5
Cellular Recognition and Adhesion
Cell surface oligosaccharides are central to cell-cell communication, cell-adhe-
sion, infection, differentiation and development. The potential for enormous
variation in glycan structure, permitting fine tuning of recognition deter-
minants, is an appealing feature of carbohydrate mediated cellular adhesion.
Furthermore, the large size of glycans allows them to cover functional sites and
hydrophobic patches in proteins, and modulate protein functions [2]. Protein-
carbohydrate interactions are employed in a number of instances of cellular
adhesion, in systems as varied as binding of pathogenic bacteria to animal cells
[113], neuronal development [114], lymphocyte homing [115], immune recog-
nition [116] and cellular migration during embryogenesis [117].It was proposed
that adhesion of these cells was caused by the interaction between glycans in
the membranes of one cell with the GlycT present in the membranes of adja-
cent cells.
The binding of viruses to host cells involves the viral hemagglutinins and the
host cell surface glycoproteins [118]. Similarly, other cell surface carbohydrates