biostudies-literatureUnknown299(6)Ruiz MThe human AdipoR2 and its Caenorhabditis elegans homolog PAQR-2 are multipass plasma membrane proteins that protect cells against membrane rigidification. However, how AdipoR2 promotes membrane fluidity mechanistically is not clear. Using 13C-labeled fatty acids, we show that AdipoR2 can promote the elongation and incorporation of membrane-fluidizing polyunsaturated fatty acids into phospholipids. To elucidate the molecular basis of these activities, we performed immunoprecipitations of tagged AdipoR2 and PAQR-2 expressed in HEK293 cells or whole C. elegans, respectively, and identified coimmunoprecipitated proteins using mass spectrometry. We found that several of the evolutionarily conserved AdipoR2/PAQR-2 interactors are important for fatty acid elongation and incorporation into phosphoThe Journal of biological chemistry104799https://www.ebi.ac.uk/biostudies/studies/S-EPMC10279913biostudies-literatureAdipoR2 recruits protein interactors to promote fatty acid elongation and membrane fluidity.PMC10279913Ruhanen HBoren JDevkota RHenricsson MKaper DBusayavalasa KPilon MKakela RRadovic URuiz MfalseAdipoR2 recruits protein interactors to promote fatty acid elongation and membrane fluidity.The human AdipoR2 and its Caenorhabditis elegans homolog PAQR-2 are multipass plasma membrane proteins that protect cells against membrane rigidification. However, how AdipoR2 promotes membrane fluidity mechanistically is not clear. Using 13C-labeled fatty acids, we show that AdipoR2 can promote the elongation and incorporation of membrane-fluidizing polyunsaturated fatty acids into phospholipids. To elucidate the molecular basis of these activities, we performed immunoprecipitations of tagged AdipoR2 and PAQR-2 expressed in HEK293 cells or whole C. elegans, respectively, and identified coimmunoprecipitated proteins using mass spectrometry. We found that several of the evolutionarily conserved AdipoR2/PAQR-2 interactors are important for fatty acid elongation and incorporation into phospho2023-01-01T00:00:00Z2023 Jun2026-04-12T23:13:30.503Z2025-04-04T11:50:09.161ZS-EPMC102799133716415410.1016/j.jbc.2023.104799