An Endosomal NAADP-Sensitive Two-Pore Ca2+ Channel Regulates ER-Endosome Membrane Contact Sites to Control Growth Factor Signaling.pdfVIP

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2017-03-16 发布于天津
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An Endosomal NAADP-Sensitive Two-Pore Ca2+ Channel Regulates ER-Endosome Membrane Contact Sites to Control Growth Factor Signaling.pdf

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An Endosomal NAADP-Sensitive Two-Pore Ca2+ Channel Regulates ER-Endosome Membrane Contact Sites to Control Growth Factor Signaling.pdf

Report An Endosomal NAADP-Sensitive Two-Pore Ca2+ Channel Regulates ER-Endosome Membrane Contact Sites to Control Growth Factor Signaling Graphical Abstract Authors Bethan S. Kilpatrick, Emily R. Eden, Leanne N. Hockey, Elizabeth Yates, Clare E. Futter, Sandip Patel Correspondence c.futter@ucl.ac.uk (C.E.F.), patel.s@ucl.ac.uk (S.P.) In Brief Endosomes form junctions with the ER, but how this contact is regulated remains unclear. Kilpatrick et al. ?nd that Ca2+ release by an endosomal ion channel facilitates inter-organellar coupling to temper signals mediated by an internalized growth factor receptor. Endosome-ER contact sites thus emerge as Ca2+-dependent signaling hubs. Highlights d NAADP/TPC1 signaling maintains endo-lysosomal morphology d TPC1 localizes to contacts between late endosomes and the endoplasmic reticulum d NAADP/TPC1 signaling regulates contact site formation d NAADP tempers EGF receptor-mediated signaling Kilpatrick et al., 2017, Cell Reports 18, 1636–1645 February 14, 2017 a 2017 The Author(s). /10.1016/j.celrep.2017.01.052 Cell Reports Report An Endosomal NAADP-Sensitive Two-Pore Ca2+ Channel Regulates ER-Endosome Membrane Contact Sites to Control Growth Factor Signaling Bethan S. Kilpatrick,1,3 Emily R. Eden,2,3 Leanne N. Hockey,1 Elizabeth Yates,1 Clare E. Futter,2,* and Sandip Patel1,4,* 1Department of Cell and Developmental Biology, University College London, London WC1E 6BT, UK 2Department of Cell Biology, Institute of Ophthalmology, University College London, London EC1V 9EL, UK 3Co-?rst author 4Lead Contact *Correspondence: c.futter@ucl.ac.uk (C.E.F.), patel.s@ucl.ac.uk (S.P.) /10.1016/j.celrep.2017.01.052 SUMMARY Membrane contact sites are regions of close apposition between organelles that facilitate information transfer. Here, we reveal an essential role for Ca2+ derived from the endo-lysosomal system in maintaining contact between endosomes and the endoplasmic reticulum (ER). Antagonizing action of the Ca2+-mobilizing messenger NAADP,