Functional and topological analysis of PSENEN, the fourth subunit of the γ-secretase complex.

ABSTRACT: The γ-secretase complexes are intramembrane cleaving proteases involved in the generation of the Aβ peptides in Alzheimer's disease. The complex consists of four subunits, with Presenilin harboring the catalytic site. Here, we study the role of the smallest subunit, PSENEN or Presenilin enhancer 2, encoded by the gene Psenen, in vivo and in vitro. We find a profound Notch deficiency phenotype in Psenen^-/- embryos confirming the essential role of PSENEN in the γ-secretase complex. We used Psenen^-/- fibroblasts to explore the structure-function of PSENEN by the scanning cysteine accessibility method. Glycine 22 and proline 27, which border the membrane domains 1 and 2 of PSENEN, are involved in complex formation and stabilization of γ-secretase. The hairpin structured h

SUBMITTER: Serneels L 

PROVIDER: S-EPMC10790097 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature