title: Association of malectin with ribophorin I is crucial for attenuation of misfolded glycoprotein secretion.
abstract: We previously demonstrated that malectin associates with ribophorin I, which is a subunit of oligosaccharyltransferase in the endoplasmic reticulum (ER). When malectin and ribophorin I are overexpressed in the ER, secretion of an α1-antitrypsin (AT) variant whose folding is defective, termed null Hong Kong (AT(NHK)), is decreased. To confirm whether the interaction between malectin and ribophorin I is involved in the decreased secretion of misfolded glycoproteins, we constructed an expression vector encoding truncated malectin, which could not associate with ribophorin I and had an Lys-Asp-Glu-Leu ER-retention sequence at its C-terminus. Expression of wild-type malectin abrogated AT(NHK) secretion, whereas expression of truncated malectin did not affect AT(NHK) secretion. Both wild-type and truncated malectin bound to AT(NHK), and the level of AT(NHK) was similar in cells expressing wild-type malectin and those expressing truncated malectin. Furthermore, we previously showed that decreased secretion of misfolded AT(NHK) by malectin overexpression is restored by treatment with a proteasome inhibitor. These results clearly demonstrate that the association of malectin with ribophorin I is required to capture misfolded glycoproteins and direct them to the degradation pathway.
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 277-8562 Chiba, Japan.
authors.forename: Koh
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 277-8562 Chiba, Japan.
authors.forename: Sheng-Ying
authors.initials: SY
authors.lastname: Qin
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 277-8562 Chiba, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Matsumoto
authors.affiliation: Department of Integrated Biosciences, Graduate School of Frontier Sciences, The University of Tokyo, 277-8562 Chiba, Japan. Electronic address: yamamoto@k.u-tokyo.ac.jp.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Yamamoto
mesh_terms: D006367:HeLa Cells; D006801:Humans; D037102:Lectins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism; D017510:Protein Folding; D060066:Protein Interaction Maps; D021382:Protein Sorting Signals; D059748:Proteolysis; D057165:Proteostasis Deficiencies / Q000235:genetics / Q000378:metabolism; D000515:alpha 1-Antitrypsin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D037102:Lectins; C554484:MLEC protein, human; D008565:Membrane Proteins; D009842:Oligopeptides; D021382:Protein Sorting Signals; D000515:alpha 1-Antitrypsin; C034241:ribophorin; C073762:lysyl-aspartyl-glutamyl-leucine
keywords: Glycoprotein quality control; Malectin; Misfolded protein; Ribophorin I