Figure 8. Model of lipid phase separation and protein segregation in membranes of saturated lipids.

Elevated lipid saturation in the membrane of ole1-20 cells generates gel-phase microdomains enriched for saturated lipids. ER proteins, including Erg1, in the saturated lipids are misfolded and targeted for ERAD through the E3 enzyme Doa10 and the E2 protein Ubc7, which is recruited by Cue1 to the ER. Additional accumulation of lanosterol by doa10Δ or Erg1(P469L) overexpression (O.E.) expands the gel phase and causes protein segregation among different phases of the membrane, resulting in the aberrant ER morphology and mislocalized and/or dysfunctional ER proteins.