Figure 6.
Model for γ-secretase sorting of substrates mediated by lipid microdomain. (a) Direct enzyme insertion followed by lipid reorganization and packing of enzyme complexes primarily in the Lo phase. (b) Subsequent incorporation and concentration of enzyme complex into the Lo phase (green) guide proteolysis by recruiting the cholesterol-rich ordered phase. Overall, the direct visualization of the phase localization of enzyme and substrates suggests a thermodynamic regulatory mechanism that manifests in the Lo/Ld sorting of enzyme and SB4(APP) shown in red and the exclusion of NTM2 (Notch2) shown in blue from the Lo phase.