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ERCOPE SIGNED

The ER located master regulation of endosomal positioning and further movements

Total Cost €

0

EC-Contrib. €

0

Partnership

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 ERCOPE project word cloud

Explore the words cloud of the ERCOPE project. It provides you a very rough idea of what is the project "ERCOPE" about.

vesicles    ubiquitin    er    homeostasis    modulated    lysosomal    outwards    interrogate    previously    times    regulation    resolve    hub    critical    diverse    moving    degradation    collective    endocytic    departures    membrane    controls    busy    sirna    cell    protein    resides    bulk    immune    serves    elucidated    release    endosomal    cloud    cells    class    bacterial    network    perinuclear    responsible    spatial    molecular    intersection    loading    positioning    dendritic    herein    implications    arrivals    compartment    biosynthetic    screen    maturation    genome    relationship    uncharacterized    infection    lies    disparate    periphery    mitotic    influencing    functions    endosomes    cytokinesis    biology    largely    unknown    function    ligase    extends    compartments    cargo    clear    biological    basis    constituent    origins    mhc    vesicular    division    signaling    proximity    resolution    catalytic    respect    entirely    poised    transport    endo    antigen    region    presentation   

Project "ERCOPE" data sheet

The following table provides information about the project.

Coordinator
ACADEMISCH ZIEKENHUIS LEIDEN 

Organization address
address: ALBINUSDREEF 2
city: LEIDEN
postcode: 2333 ZA
website: www.lumc.nl

contact info
title: n.a.
name: n.a.
surname: n.a.
function: n.a.
email: n.a.
telephone: n.a.
fax: n.a.

 Coordinator Country Netherlands [NL]
 Project website https://www.lumc.nl/research/grants-and-support/ERC/
 Total cost 2˙383˙625 €
 EC max contribution 2˙383˙625 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2015-AdG
 Funding Scheme ERC-ADG
 Starting year 2016
 Duration (year-month-day) from 2016-09-01   to  2021-08-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    ACADEMISCH ZIEKENHUIS LEIDEN NL (LEIDEN) coordinator 2˙383˙625.00

Map

 Project objective

The endo-lysosomal system is critical to diverse processes, including protein homeostasis, signaling and antigen presentation. The vesicular compartment is organized as a collective unit wherein the bulk of endosomes derived from disparate origins resides in a cloud in the perinuclear region and extends outwards to include quickly moving vesicles in the periphery. At this busy intersection between the endocytic and biosynthetic pathways, lies the late endosomal compartment, responsible for protein degradation and antigen processing. In dendritic and other immune cells, this major constituent of the perinuclear cloud serves as a hub for MHC class II antigen loading. Previous work by us and others has elucidated key elements of MHC class II biology through the study of late endosomal transport to and from the cell periphery. It is clear that cell biology of endosomes is modulated by their proximity to other membrane compartments during transport, maturation, cargo selection and delivery and even during cytokinesis in cell division. However, how endosomal positioning in the perinuclear cloud and how their release for further transport is controlled remains largely unknown. The aim of this proposal is to define the molecular basis for endosomal positioning and then to interrogate the relationship between spatial regulation of the endocytic compartment and its functions with respect to i) MHC class II antigen presentation, ii) bacterial infection and iii) mitotic resolution. From a genome-wide siRNA screen for factors influencing MHC class II biology, we have identified a unique and previously uncharacterized ubiquitin ligase that resides in the ER membrane, from where it controls endosomal positioning and times their arrivals and departures as a function of its catalytic activity. On this basis, the work proposed herein is poised to resolve an entirely new molecular network in control of endosomal biology with implications for diverse biological processes.

 Publications

year authors and title journal last update
List of publications.
2016 Wijdeven RH, Janssen H, Nahidiazar L, Janssen L, Jalink K, Berlin I, Neefjes J
Cholesterol and ORP1L-mediated ER contact sites control autophagosome transport and fusion with the endocytic pathway
published pages: , ISSN: 2041-1723, DOI:
Nat Commun. 2019-06-13
2016 Rock KL, Reits E, Neefjes J
Present Yourself! By MHC Class I and MHC Class II Molecules
published pages: , ISSN: 1471-4906, DOI:
Trends Immunol. 2019-06-13
2017 Gagnaire A, Nadel B, Raoult D, Neefjes J, Gorvel JP
Collateral damage: insights into bacterial mechanisms that predispose host cells to cancer
published pages: , ISSN: 1740-1526, DOI:
Nat Rev Microbiol. 2019-06-13
2018 Luimstra JJ, Garstka MA, Roex MCJ, Redeker A, Janssen GMC, van Veelen PA, Arens R, Falkenburg JHF, Neefjes J, Ovaa H
A flexible MHC class I multimer loading system for large-scale detection of antigen-specific T cells
published pages: , ISSN: 0022-1007, DOI:
J Exp Med. 2019-06-13
2016 Jongsma ML, Berlin I, Wijdeven RH, Janssen L, Janssen GM, Garstka MA, Janssen H, Mensink M, van Veelen PA, Spaapen RM, Neefjes J
An ER-Associated Pathway Defines Endosomal Architecture for Controlled Cargo Transport
published pages: , ISSN: 2451-9456, DOI:
Cell. 2019-06-13
2018 Wijdeven RH, van Luijn MM, Wierenga-Wolf AF, Akkermans JJ, van den Elsen PJ, Hintzen RQ, Neefjes J
Chemical and genetic control of IFNγ-induced MHCII expression
published pages: , ISSN: 1469-221X, DOI:
EMBO Rep. 2019-06-13
2017 Bakker J, Spits M, Neefjes J, Berlin I
The EGFR odyssey - from activation to destruction in space and time
published pages: , ISSN: 0021-9533, DOI:
J Cell Sci. 2019-06-13
2018 Mulder MPC, Merkx R, Witting KF, Hameed DS, El Atmioui D, Lelieveld L, Liebelt F, Neefjes J, Berlin I, Vertegaal ACO, Ovaa H
Total Chemical Synthesis of SUMO and SUMO-Based Probes for Profiling the Activity of SUMO-Specific Proteases
published pages: , ISSN: 1433-7851, DOI:
Angew Chem Int Ed Engl. 2019-06-13
2018 Borg Distefano M, Haugen LH, Wang Y, Perdreau-Dahl H, Kjos I, Jia D, Morth JP, Neefjes J, Bakke O, Progida C
TBC1D5 controls the GTPase cycle of Rab7b
published pages: , ISSN: 0021-9533, DOI:
J Cell Sci. 2019-06-13
2018 Cabukusta B, Neefjes J
Mechanisms of lysosomal positioning and movement
published pages: , ISSN: 1398-9219, DOI:
Traffic 2019-06-13
2017 Bonifacino JS, Neefjes J
Moving and positioning the endolysosomal system
published pages: , ISSN: 0955-0674, DOI:
Curr Opin Cell Biol. 2019-06-13
2018 Mughini-Gras L, Schaapveld M, Kramers J, Mooij S, Neefjes-Borst EA, Pelt WV, Neefjes J
Increased colon cancer risk after severe Salmonella infection
published pages: , ISSN: 1932-6203, DOI:
PLoS One 2019-06-13

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