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 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.
Ayalon-Soffer
M
M
Department of Cell Research and Immunology, George Wise Faculty of Life Sciences, Tel Aviv University, Israel.
Kamhi-Nesher
S
S
Lederkremer
G Z
GZ
D016475:3T3 Cells; D017398:Alternative Splicing; D000818:Animals; D037263:Asialoglycoprotein Receptor; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009097:Multienzyme Complexes / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex; D011487:Protein Conformation; D017510:Protein Folding; D011498:Protein Precursors / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000378:metabolism*
D037263:Asialoglycoprotein Receptor; D008565:Membrane Proteins; D009097:Multienzyme Complexes; D011498:Protein Precursors; D011956:Receptors, Cell Surface; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex