biostudies-literatureEden ERMedical Research CouncilWellcome Trust473-83https://www.ebi.ac.uk/biostudies/studies/S-EPMC4906250biostudies-literatureUnknown37(5)Membrane contact sites between the ER and multivesicular endosomes/bodies (MVBs) play important roles in endosome positioning and fission and in neurite outgrowth. ER-MVB contacts additionally function in epidermal growth factor receptor (EGFR) tyrosine kinase downregulation by providing sites where the ER-localized phosphatase, PTP1B, interacts with endocytosed EGFR before the receptor is sorted onto intraluminal vesicles (ILVs). Here we show that these contacts are tethered by annexin A1 and its Ca(2+)-dependent ligand, S100A11, and form a subpopulation of differentially regulated contact sites between the ER and endocytic organelles. Annexin A1-regulated contacts function in the transfer of ER-derived cholesterol to the MVB when low-density lipoprotein-cholesterol in endosomes is low. TDevelopmental cellAnnexin A1 Tethers Membrane Contact Sites that Mediate ER to Endosome Cholesterol Transport.PMC4906250G0801878M010767093445MR/M010767/1Eden ERTsapara ASobota ASanchez-Heras ELevine TPFutter CEfalseAnnexin A1 Tethers Membrane Contact Sites that Mediate ER to Endosome Cholesterol Transport.Membrane contact sites between the ER and multivesicular endosomes/bodies (MVBs) play important roles in endosome positioning and fission and in neurite outgrowth. ER-MVB contacts additionally function in epidermal growth factor receptor (EGFR) tyrosine kinase downregulation by providing sites where the ER-localized phosphatase, PTP1B, interacts with endocytosed EGFR before the receptor is sorted onto intraluminal vesicles (ILVs). Here we show that these contacts are tethered by annexin A1 and its Ca(2+)-dependent ligand, S100A11, and form a subpopulation of differentially regulated contact sites between the ER and endocytic organelles. Annexin A1-regulated contacts function in the transfer of ER-derived cholesterol to the MVB when low-density lipoprotein-cholesterol in endosomes is low. T2016-01-01T00:00:00Z2016 Jun2026-05-05T16:17:38.774Z2019-03-27T02:15:58ZS-EPMC49062502727004210.1016/j.devcel.2016.05.005