The AdipoR2 protein recruits an ER-localized fatty acid elongation complex to promote membrane homeostasis

The human AdipoR2 protein and its C. elegans homolog PAQR-2 are multi-pass plasma membrane proteins that protect cells against membrane rigidification. We seek to better understand the mechanisms by which these proteins can promote the synthesis and incorporation of membrane-fluidizing unsaturated fatty acids into phospholipids. To this end, we performed immunoprecipitations of tagged AdipoR2 and PAQR-2 expressed in HEK293 cells or whole C. elegans, respectively, and identified co-immunoprecipitated proteins using mass spectroscopy. Among the conserved interaction partners, we identified many proteins likely important for the protein life cycles (e.g. ribosome, proteasome, vesicle trafficking components). Importantly, several proteins important for fatty acid synthesis, elongation and incorporation into phospholipids were also identified as evolutionarily conserved AdipoR2/PAQR-2 interaction partners. We experimentally verified several of these interactions, and propose that AdipoR2 and PAQR-2 can recruit an ER-bound membrane complex to promote the production and incorporation of unsaturated fatty acids into phospholipids.