Differential Modes of Orphan Subunit Recognition for the WRB/CAML Complex

• DOI: 10.1016/j.celrep.2020.02.084
• Publication Date: 2020-03-17T14:40:24Z
• Authors: Alison J. Inglis; Katharine R. Page; Alina Guna; Rebecca M. Voorhees
• Keywords: 0303 health sciences; QH301-705.5; Protein Stability; 610; Nuclear Proteins; membrane proteins; Endoplasmic Reticulum; Article; endoplasmic reticulum; Protein Subunits; 03 medical and health sciences; Dogs; HEK293 Cells; Multiprotein Complexes; Proteolysis; Animals; Humans; oligomeric assembly; Rabbits; quality control; Biology (General); Ribosomes; Adaptor Proteins, Signal Transducing; Protein Binding

A large proportion of membrane proteins must be assembled into oligomeric complexes for function. How this process occurs is poorly understood, but it clear that complex assembly tightly regulated to avoid accumulation orphan subunits with potential cytotoxic effects. We interrogated in mammalian cells by using the WRB/CAML complex, an essential insertase tail-anchored endoplasmic reticulum (ER), as a model system. Our data suggest stability each subunit differentially regulated. In WRB's absence, CAML folds incorrectly, causing aberrant exposure hydrophobic transmembrane domain ER lumen. When present, WRB can correct topology both vitro and cells. contrast, independently fold correctly still degraded absence CAML. therefore propose there are at least two distinct regulatory pathways surveillance ER.