PMID- 27270042 OWN - NLM STAT- MEDLINE DCOM- 20170612 LR - 20220129 IS - 1878-1551 (Electronic) IS - 1534-5807 (Print) IS - 1534-5807 (Linking) VI - 37 IP - 5 DP - 2016 Jun 6 TI - Annexin A1 Tethers Membrane Contact Sites that Mediate ER to Endosome Cholesterol Transport. PG - 473-83 LID - S1534-5807(16)30282-9 [pii] LID - 10.1016/j.devcel.2016.05.005 [doi] AB - 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. This sterol traffic depends on interaction between ER-localized VAP and endosomal oxysterol-binding protein ORP1L, and is required for the formation of ILVs within the MVB and thus for the spatial regulation of EGFR signaling. CI - Copyright (c) 2016 The Author(s). Published by Elsevier Inc. All rights reserved. FAU - Eden, Emily R AU - Eden ER AD - UCL Institute of Ophthalmology, London EC1V 9EL, UK. FAU - Sanchez-Heras, Elena AU - Sanchez-Heras E AD - UCL Institute of Ophthalmology, London EC1V 9EL, UK. FAU - Tsapara, Anna AU - Tsapara A AD - UCL Institute of Ophthalmology, London EC1V 9EL, UK; Technical University of Crete, 73100 Chania, Greece. FAU - Sobota, Andrzej AU - Sobota A AD - Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland. FAU - Levine, Tim P AU - Levine TP AD - UCL Institute of Ophthalmology, London EC1V 9EL, UK. FAU - Futter, Clare E AU - Futter CE AD - UCL Institute of Ophthalmology, London EC1V 9EL, UK. Electronic address: c.futter@ucl.ac.uk. LA - eng GR - 093445/Wellcome Trust/United Kingdom GR - G0801878/MRC_/Medical Research Council/United Kingdom GR - MR/M010767/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PL - United States TA - Dev Cell JT - Developmental cell JID - 101120028 RN - 0 (Annexin A1) RN - 0 (Lipoproteins, LDL) RN - 0 (Receptors, Steroid) RN - 0 (VAPA protein, human) RN - 0 (VAPB protein, human) RN - 0 (Vesicular Transport Proteins) RN - 0 (oxysterol binding protein) RN - 62229-50-9 (Epidermal Growth Factor) RN - 97C5T2UQ7J (Cholesterol) RN - EC 2.7.10.1 (ErbB Receptors) RN - EC 3.1.3.48 (PTPN1 protein, human) RN - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 1) SB - IM MH - Annexin A1/*metabolism MH - Biological Transport/drug effects MH - Cholesterol/*metabolism MH - Endocytosis/drug effects MH - Endoplasmic Reticulum/drug effects/*metabolism/ultrastructure MH - Endosomes/drug effects/*metabolism/ultrastructure MH - Epidermal Growth Factor/pharmacology MH - ErbB Receptors/metabolism MH - HeLa Cells MH - Humans MH - Lipoproteins, LDL/pharmacology MH - Multivesicular Bodies/drug effects/metabolism/ultrastructure MH - Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism MH - Receptors, Steroid/metabolism MH - Transport Vesicles/drug effects/metabolism MH - Vesicular Transport Proteins/metabolism PMC - PMC4906250 EDAT- 2016/06/09 06:00 MHDA- 2016/06/09 06:01 PMCR- 2016/06/06 CRDT- 2016/06/09 06:00 PHST- 2015/07/01 00:00 [received] PHST- 2016/04/11 00:00 [revised] PHST- 2016/05/09 00:00 [accepted] PHST- 2016/06/09 06:00 [entrez] PHST- 2016/06/09 06:00 [pubmed] PHST- 2016/06/09 06:01 [medline] PHST- 2016/06/06 00:00 [pmc-release] AID - S1534-5807(16)30282-9 [pii] AID - 10.1016/j.devcel.2016.05.005 [doi] PST - ppublish SO - Dev Cell. 2016 Jun 6;37(5):473-83. doi: 10.1016/j.devcel.2016.05.005.