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

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 foldin...

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Bibliographic Details
Published in:FEBS letters 1999-10, Vol.460 (1), p.112-116
Main Authors: Ayalon-Soffer, Michal, Kamhi-Nesher, Shiri, Lederkremer, Gerardo Z
Format: Article
Language:English
Subjects:
3T3 Cells
ALLN, N-acetyl-leucyl-leucyl-norleucinal
Alternative Splicing
Animals
ASGPR, asialoglycoprotein receptor
Asialoglycoprotein Receptor
Assembly
BiP, heavy chain binding protein
Cysteine Endopeptidases - metabolism
DTT, dithiothreitol
Endoplasmic Reticulum - metabolism
Endoplasmic reticulum degradation
Folding
Membrane Proteins - metabolism
MG-132, N-carbobenzoxyl-leucinyl-leucinyl-leucinal
Mice
Multienzyme Complexes - metabolism
Proteasome
Proteasome Endopeptidase Complex
Protein Conformation
Protein Folding
Protein Precursors - metabolism
Receptors, Cell Surface - metabolism
T cell receptor
UPR, unfolded protein response
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Summary: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.
ISSN:0014-5793
1873-3468
DOI:10.1016/S0014-5793(99)01321-6