Folding and self‐assembly do not prevent ER retention and proteasomal degradation of asialoglycoprotein receptor H2a

FEBS Letters

Kamhi-Nesher, Shiri¹  Lederkremer, Gerardo Z¹  Ayalon-Soffer, Michal¹ 

[1] Department of Cell Research and Immunology, George Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv 69978, Israel

关键词: Endoplasmic reticulum degradation;    Proteasome;    Asialoglycoprotein receptor;    T cell receptor;    Assembly;    Folding;    ASGPR;    asialoglycoprotein receptor;    ALLN;    N-acetyl-leucyl-leucyl-norleucinal;    MG-132;    N-carbobenzoxyl-leucinyl-leucinyl-leucinal;    DTT;    dithiothreitol;    BiP;    heavy chain binding protein;    UPR;    unfolded protein response;   

DOI  :  10.1016/S0014-5793(99)01321-6

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The human asialoglycoprotein receptor H2a precursor, a type II membrane protein, is cleaved to a soluble form that is secreted. Uncleaved precursor molecules are completely retained in the endoplasmic reticulum (ER) and degraded by the proteasome. To find out the causes of its fate we studied folding of H2a precursor, which was very similar to that of its alternatively spliced variant H2b which can exit to the Golgi. Proteasomal inhibition led to accumulation of folded rather than unfolded molecules. Accumulation of ER-retained H2a did not cause an unfolded protein response. Although the receptor is a heterooligomer of the H1 and H2 subunits, single expression led to some self-assembly. Whereas these homooligomers accumulated for H2b they were degraded for H2a. Translocation of H2a into the ER occurred efficiently. Therefore, the retention and proteasomal degradation of uncleaved membrane-bound H2a precursor from the ER do not involve aberrant translocation or misfolding and are not prevented by self-assembly.

【 授权许可】

Unknown