γ-secretase facilitates retromer-mediated retrograde transport.

ABSTRACT: Retromer mediates retrograde transport of protein cargoes from endosomes to the trans-Golgi network (TGN). γ-secretase is a protease that cleaves the transmembrane domain of its target proteins. Although retromer can form a stable complex with γ-secretase, the functional consequences of this interaction are not known. Here, we report that retromer-mediated retrograde protein trafficking in cultured human epithelial cells is impaired by the γ-secretase inhibitor XXI or by knockout of PS1 (also known as PSEN1), the catalytic subunit of γ-secretase. These treatments inhibited endosome-to-TGN trafficking of retromer-dependent retrograde cellular cargoes, divalent metal transporter 1 isoform II, cation-independent mannose-6-phosphate receptor and shiga toxin, whereas trafficking of retromer-ind

SUBMITTER: Takeo Y 

PROVIDER: S-EPMC11883284 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature