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PMID: 27270042 Published · ppublish English Journal Article

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

Developmental cell ·Vol. 37 ·No. 5 ·2016-06-06 ·Pages 473-83

Eden ER, Sanchez-Heras E, Tsapara A, Sobota A, Levine TP, Futter CE

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 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.

MeSH Terms
Annexin A1/metabolism Biological Transport/drug effects Cholesterol/metabolism Endocytosis/drug effects Endoplasmic Reticulum/drug effects,metabolism,ultrastructure Endosomes/drug effects,metabolism,ultrastructure Epidermal Growth Factor/pharmacology ErbB Receptors/metabolism HeLa Cells Humans Lipoproteins, LDL/pharmacology Multivesicular Bodies/drug effects,metabolism,ultrastructure Protein Tyrosine Phosphatase, Non-Receptor Type 1/metabolism Receptors, Steroid/metabolism Transport Vesicles/drug effects,metabolism Vesicular Transport Proteins/metabolism
Chemicals
Annexin A1 Lipoproteins, LDL Receptors, Steroid VAPA protein, human VAPB protein, human Vesicular Transport Proteins oxysterol binding protein Epidermal Growth Factor Cholesterol ErbB Receptors PTPN1 protein, human Protein Tyrosine Phosphatase, Non-Receptor Type 1
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Eden Emily R
UCL Institute of Ophthalmology, London EC1V 9EL, UK.
Sanchez-Heras Elena
UCL Institute of Ophthalmology, London EC1V 9EL, UK.
Tsapara Anna
UCL Institute of Ophthalmology, London EC1V 9EL, UK; Technical University of Crete, 73100 Chania, Greece.
Sobota Andrzej
Nencki Institute of Experimental Biology, 02-093 Warsaw, Poland.
Levine Tim P
UCL Institute of Ophthalmology, London EC1V 9EL, UK.
Futter Clare E
UCL Institute of Ophthalmology, London EC1V 9EL, UK. Electronic address: [email protected].
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Article Info
Journal
Developmental cell
Abbr.
Dev Cell
ISSN
1878-1551
DOI
10.1016/j.devcel.2016.05.005
Email
[email protected]
Published
2016-06-06
Pages
473-83
Language
English
Region
United States
NLM ID
101120028
PMCID
PMC4906250
Subset
IM
Grants
Wellcome Trust · 093445 · United Kingdom
Medical Research Council · G0801878 · United Kingdom
Medical Research Council · MR/M010767/1 · United Kingdom
External Links
PubMed source DOI: 10.1016/j.devcel.2016.05.005 PMC Full Text View journal details
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