A luminescent reporter assay to quantify SORL1 ectodomain shedding and retromer-dependent endosome recycling activity.

ABSTRACT: Growing evidence suggests that defects in endosomal recycling are a causal mechanism for Alzheimer's disease (AD). Sortilin-like receptor 1 (SORL1) is an endosomal sorting receptor that acts together with the retromer complex to facilitate shuttling of cargo from endosomes back to the trans-Golgi network or to the cell surface. Accumulating data indicate that SORL1 dysfunction contributes to AD pathogenesis. SORL1 is trafficked from the endosome to the cell surface in a retromer-dependent process, where it undergoes enzymatic cleavage, resulting in shedding of the SORL1 ectodomain (also known as soluble SORL1). We capitalized on this physiological process to develop and validate a cell-based luminescent reporter assay incorporating enhanced Gaussia luciferase (eGLuc) to quantify soluble SO

SUBMITTER: Fazeli E 

PROVIDER: S-EPMC12860930 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature