Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 454, Issue 3, Pages 436-440Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2014.10.102
Keywords
Malectin; Ribophorin I; Glycoprotein quality control; Misfolded protein
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Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan [24390015, 24659026, 25117710]
- Naito Foundation
- Grants-in-Aid for Scientific Research [25117710, 24659026] Funding Source: KAKEN
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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 alpha 1-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 ATNHK secretion, whereas expression of truncated malectin did not affect ATNHK secretion. Both wild-type and truncated malectin bound to ATNHK, and the level of ATNHK was similar in cells expressing wild-type malectin and those expressing truncated malectin. Furthermore, we previously showed that decreased secretion of misfolded ATNHK 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. (C) 2014 Elsevier Inc. All rights reserved.
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