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Annexin A1 Tethers Membrane Contact Sites that Mediate ER to Endosome Cholesterol Transport

Eden, ER; Sanchez-Heras, E; Tsapara, A; Sobota, A; Levine, TP; Futter, CE; (2016) Annexin A1 Tethers Membrane Contact Sites that Mediate ER to Endosome Cholesterol Transport. Developmental Cell , 37 (5) pp. 473-483. 10.1016/j.devcel.2016.05.005. Green open access

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Abstract

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 Ca2+-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.

Type: Article
Title: Annexin A1 Tethers Membrane Contact Sites that Mediate ER to Endosome Cholesterol Transport
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.devcel.2016.05.005
Publisher version: http://dx.doi.org/10.1016/j.devcel.2016.05.005
Language: English
Additional information: Copyright © 2016 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Science & Technology, Life Sciences & Biomedicine, Cell Biology, Developmental Biology, GROWTH-FACTOR RECEPTOR, PERFRINGOLYSIN O, PROTEIN VAP, BINDING, PROBE, TRAFFICKING, ASSOCIATION, CELLS, GOLGI, CA2+
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
URI: https://discovery.ucl.ac.uk/id/eprint/1499852
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