Conserved LIR-specific interaction of Sigma-1 receptor and GABARAP.

ABSTRACT: Among its various functions, the sigma-1 receptor (σ1R) has been reported to modulate macroautophagy. It is currently unknown how this activity is mediated. We phylogenetically, structurally, and biochemically analyzed σ1R regarding its function in autophagy. We identified several putative LC3-interacting-regions (LIRs) that may mediate interactions with ATG8 proteins, which are known to promote autophagosome biogenesis, autophagic cargo reception, and lysosome fusion. Human σ1R comprises a LIR motif (hLIR5) typical for interaction with a specific ATG8, GABARAP. Biochemically, we uncovered a GABARAP-σ1R interaction depending on this motif via peptide array analysis and confirmed this via immunoprecipitation, co-localization, and proximity ligation assays. In addition, we verified a LIR-dep

SUBMITTER: Baeken MW 

PROVIDER: S-EPMC12398221 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature