Mannose 6-phosphate receptor homology domain-containing lectins in mammalian endoplasmic reticulum-associated degradation.
Quality control of glycoproteins synthesized in the endoplasmic reticulum (ER) is mediated by lectins and molecular chaperones. N-linked Glc(3)Man(9)GlcNAc(2) oligosaccharides attached to the nascent polypeptides are processed and recognized by lectins in the ER. OS-9 and XTP3-B/Erlectin, mannose 6-phosphate receptor homology (MRH) domain-containing lectins in mammals, were recently identified as ER luminal glycoproteins that participate in ER-associated degradation (ERAD) of misfolded proteins. Frontal affinity chromatography (FAC) and cell-surface expressed lectin assay revealed that both OS-9 and XTP3-B recognize high-mannose type N-glycans that lack the terminal mannose on the C branch. Furthermore, these lectins associate with the HRD1-SEL1L ubiquitin ligase complex on the ER membrane. In this chapter, we describe the FAC methods used to analyze the carbohydrate-recognition specificity of OS-9 and methods to examine the interaction and the effect on ERAD of these proteins in vivo. We also discuss the structure and function of OS-9 and XTP3-B, and the effect of these lectins on ERAD.
Hosokawa
Nobuko
N
Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto, Japan.
Kato
Koichi
K
Kamiya
Yukiko
Y
D000595:Amino Acid Sequence; D000818:Animals; D002623:Chemistry Techniques, Analytical / Q000379:methods; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology*; D008322:Mammals / Q000378:metabolism; D008954:Models, Biological; D008969:Molecular Sequence Data; D010802:Phylogeny; D011499:Protein Processing, Post-Translational / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D017527:Receptor, IGF Type 2 / Q000737:chemistry* / Q000378:metabolism / Q000502:physiology; D020539:Sequence Analysis, Protein / Q000379:methods; D017386:Sequence Homology, Amino Acid
D037102:Lectins; D017527:Receptor, IGF Type 2