C1orf115 interacts with clathrin adaptors to undergo endocytosis and induces ABCA1 to promote enteric cholesterol efflux.

ABSTRACT: C1orf115 has been identified in high-throughput screens as a regulator of multidrug resistance possibly mediated through an interaction with ATP-dependent membrane transporter ABCB1. Here we show that C1orf115 not only shares structural similarities with FACI/C11orf86 to interact with clathrin adaptors to undergo endocytosis, but also induces ABCA1 transcription to promote cholesterol efflux. C1orf115 consists of an N-terminal intrinsically disordered region and a C-terminal α-helix. Its α-helix binds to phosphoinositides, and mediates C1orf115 localization to the plasma membrane, nucleolus and nuclear speckles. An acidic dileucine-like motif "ExxxIL" within C1orf115 binds with the AP2 complex and mediates its localization to clathrin-coating pits. The positively charged amphipathic α-heli

SUBMITTER: Kang XZ 

PROVIDER: S-EPMC11757849 | biostudies-literature | 2025 Jan

REPOSITORIES: biostudies-literature