γ-Secretase Partitioning into Lipid Bilayers Remodels Membrane Microdomains after Direct Insertion.

ABSTRACT: γ-Secretase is a multisubunit complex that catalyzes intramembranous cleavage of transmembrane proteins. The lipid environment forms membrane microdomains that serve as spatio-temporal platforms for proteins to function properly. Despite substantial advances in the regulation of γ-secretase, the effect of the local membrane lipid microenvironment on the regulation of γ-secretase is poorly understood. Here, we characterized and quantified the partitioning of γ-secretase and its substrates, the amyloid precursor protein (APP) and Notch, into lipid bilayers using solid-supported model membranes. Notch substrate is preferentially localized in the liquid-disordered (L_d) lipid domains, whereas APP and γ-secretase partition as single or higher complex in both phases but highly favor th

SUBMITTER: Barros M 

PROVIDER: S-EPMC7887708 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature