Earticle

초록

영어

The cloning of glucosidase II (1) permitted the identification of a glyco-code promoting protein folding (2) and another one for dislocation of misfolded glycoproteins to degradation (3). Based on these works, EDEM1 (yeast ortholog Htm1p) was discovered and shown to be a lectin-like glycoprotein directing terminally misfolded glycoproteins for degradation (4,5). Endogenous EDEM1 existed mainly as a soluble glycoprotein and was sequestered in buds forming along rough ER cisternae outside of the transitional ER (6). This resulted in the formation of ~150 nm vesicles in the cytoplasm lacking a recognizable COP I or II coat. Surprisingly, EDEM1 in the cytosol became de-glycosylated and formed detergent-insoluble aggregates that were degraded by autophagy and not be proteasomes (7). EDEM1 vesicles also containedmisfolded Hong Kong variant of -1-antitrypsin (6). Together, these findings demonstrated the existence of a novel vesicular pathway out of the rough ER to remove misfolded luminal glycoproteins for subsequent proteasomal degradation. When the fate of incompletely assembled fibrinogen was studied (8), we made the following observations. Naturally occurring Aa-g assembly intermediates of fibrinogen were substrate for EDEM1 and exited the ER in EDEM1 vesicles. In contrast to the proteasomal degradation of free single chains, surplus Aa-g assembly intermediates of fibrinogen formed detergent-insoluble cytosolic aggregates that were degraded by autophagy. In summary, EDEM1 dislocates not only misfolded glycoproteins but also an assembly intermediate of an oligomeric glycoprotein. This indicates that ER-to-cytosol dislocation of such EDEM1 substrates occurs by a vesicular mechanism rather than by a channel of the ER membrane. Depending on the propensity of the glycoprotein to form aggregates in the cytosol. proteasomal degradation or autophagic elimination ensues.

저자

• Jürgen Roth [ Department of Biomedical Science, WCU program of Graduate School, Yonsei University ]

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간행물

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• 간행물명

  한국당과학회 학술대회

• 간기

  연간

• 수록기간

  2006~2022

• 십진분류

  KDC 517 DDC 614