Nanoscale organization of Nicastrin, the substrate receptor of the γ-secretase complex, as independent molecular domains.

ABSTRACT: Alterations in the canonical processing of Amyloid Precursor Protein generate proteoforms that contribute to the onset of Alzheimer's Disease. Modified composition of γ-secretase or mutations in its subunits has been directly linked to altered generation of Amyloid beta. Despite biochemical evidence about the role of γ-secretase in the generation of APP, the molecular origin of how spatial heterogeneity in the generation of proteoforms arises is not well understood. Here, we evaluated the localization of Nicastrin, a γ-secretase subunit, at nanometer sized functional zones of the synapse. With the help of super resolution microscopy, we confirm that Nicastrin is organized into nanodomains of high molecular density within an excitatory synapse. A similar nanoorganization was also observed f

SUBMITTER: Kedia S 

PROVIDER: S-EPMC8515736 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature