Intracellular Lectins Involved in Folding and Transport in the Endoplasmic Reticulum

Abstract

Glycosylation is a highly sophisticated post-translational modification of proteins that occurs in the endoplasmic reticulum (ER) and the Golgi apparatus. The vital biological functions served by protein glycosylation can be separated into two types. The first is the role of glycosylation in the extracellular environment, where a variety of sugar chains participate in protein secretion and stability, cell-cell adhesion and signaling, innate immunity, embryogenesis, and morphogenesis. Another role is in quality control of glycoproteins in the ER, a topic that has received recent attention. Quality control of glycoproteins is categorized into three kinds of reactions; the first is folding of newly synthesized glycoproteins, the second is ER-associated degradation of terminally misfolded or unassembled glycoproteins, and the last is sorting and transport of glycoproteins between organelles. In all three processes, N-glycans on the glycoproteins are used as tags to initiate the reactions. The process of glycosylation is conserved in yeast, plants, invertebrates and vertebrates, including mammals. Here, I focus on the intracellular lectins that participate in these processes and discuss the role of glycosylation based on the structural differences of N-glycans.

Homozygous missense mutation in theLMAN2Lgene segregates with intellectual disability in a large consanguineous Pakistani family

“…LMAN2L, also named VIPL, is a transmembrane protein located at the ER (figure 3E),29 which plays a role in the quality control of glycoproteins. It functions as a cargo receptor for glycoproteins and is expected to regulate the exchange of folded and misfolded glycoproteins for transport to the Golgi or to the ubiquitin-proteasome pathway, respectively 30 31. Different studies have shown that the substitution of a single amino acid can switch the sugar-binding affinity32 and thereby impair protein function.…”

Alteration and localization of glycan‐binding proteins in human hepatic stellate cells during liver fibrosis

“…CRDs in vertebrate lectins can be classified in families with well‐established types: intracellular lectins (calnexin family, M‐type, L‐type, and P‐type, located in luminal compartments of the secretory pathway and function in the trafficking, sorting, and targeting of glycoproteins) , and extracellular lectins (C‐type, R‐type, siglecs, and galectins) . The latter are either secreted into the extracellular matrix or body fluids or localized to the plasma membrane, and mediate a range of functions including cell adhesion and signaling, pathogen recognition, and glycoprotein clearance . Interestingly, the galectin family of lectins in animals are also high‐abundance cytoplasmic proteins, as large pools of these proteins are soluble in the cytoplasm, probably as precursors of those later secreted to the pericellular matrix [1, 43].…”

Roles for major histocompatibility complex glycosylation in immune function

“…Similar to other glycoproteins, early glucose trimming of the newly attached Glc 3 Man 9 GlcNAc 2 N -glycan core facilitates proper interactions with the lectin chaperones calnexin and calreticulin, which are involved in the chaperone-assisted protein folding and assembly pathway. Additional lectins can also contribute to this protein quality control pathway and transport from ER to Golgi [15]. Following correct protein folding and molecular assembly (i.e., β2-microglobulin and peptide antigen binding in the case of MHCIa), the N -glycan is further modified as it moves through the Golgi.…”