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.
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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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