Association of malectin with ribophorin I is crucial for attenuation of misfolded glycoprotein secretion

作者：Takeda Koh; Qin Sheng Ying; Matsumoto Naoki; Yamamoto Kazuo^*

来源：Biochemical and Biophysical Research Communications, 2014, 454(3): 436-440.

DOI：10.1016/j.bbrc.2014.10.102

• Malectin
• Ribophorin I
• Glycoprotein quality control
• Misfolded protein

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.

• 出版日期2014-11-21