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RobustSynapses SIGNED

Maintaining synaptic function for a healthy brain: Membrane trafficking and autophagy in neurodegeneration

Total Cost €

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EC-Contrib. €

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Project "RobustSynapses" data sheet

The following table provides information about the project.

Coordinator
VIB 

Organization address
address: RIJVISSCHESTRAAT 120
city: ZWIJNAARDE - GENT
postcode: 9052
website: www.vib.be

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 Belgium [BE]
 Total cost 1˙999˙025 €
 EC max contribution 1˙999˙025 € (100%)
 Programme 1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
 Code Call ERC-2014-CoG
 Funding Scheme ERC-COG
 Starting year 2016
 Duration (year-month-day) from 2016-01-01   to  2020-12-31

 Partnership

Take a look of project's partnership.

# participants  country  role  EC contrib. [€] 
1    VIB BE (ZWIJNAARDE - GENT) coordinator 1˙999˙025.00

Map

 Project objective

Neurodegeneration is characterized by misfolded proteins and dysfunctional synapses. Synapses are often located very far away from their cell bodies and they must therefore largely independently cope with the unfolded, dysfunctional proteins that form as a result of synaptic activity and stress. My hypothesis is that synaptic terminals have adopted specific mechanisms to maintain robustness over their long lives and that these may become disrupted in neurodegenerative diseases. Recent evidence indicates an intriguing relationship between several Parkinson disease genes, synaptic vesicle trafficking and autophagy, providing an excellent entry point to study key molecular mechanisms and interactions in synaptic membrane trafficking and synaptic autophagy. We will use novel genome editing methodologies enabling fast in vivo structure-function studies in fruit flies and we will use differentiated human neurons to assess the conservation of mechanisms across evolution. In a complementary approach I also propose to capitalize on innovative in vitro liposome-based proteome-wide screening methods as well as in vivo genetic screens in fruit flies to find novel membrane-associated machines that mediate synaptic autophagy with the ultimate aim to reveal how these mechanisms regulate the maintenance of synaptic health. Our work not only has the capacity to uncover novel aspects in the regulation of presynaptic autophagy and function, but it will also reveal mechanisms of synaptic dysfunction in models of neuronal demise and open new research lines on mechanisms of synaptic plasticity.

 Publications

year authors and title journal last update
List of publications.
2016 Sandra-Fausia Soukup, Sabine Kuenen, Roeland Vanhauwaert, Julia Manetsberger, Sergio Hernández-Díaz, Jef Swerts, Nils Schoovaerts, Sven Vilain, Natalia V. Gounko, Katlijn Vints, Ann Geens, Bart De Strooper, Patrik Verstreken
A LRRK2-Dependent EndophilinA Phosphoswitch Is Critical for Macroautophagy at Presynaptic Terminals
published pages: 829-844, ISSN: 0896-6273, DOI: 10.1016/j.neuron.2016.09.037
Neuron 92/4 2019-05-30
2017 Lujia Zhou, Joseph McInnes, Keimpe Wierda, Matthew Holt, Abigail G. Herrmann, Rosemary J. Jackson, Yu-Chun Wang, Jef Swerts, Jelle Beyens, Katarzyna Miskiewicz, Sven Vilain, Ilse Dewachter, Diederik Moechars, Bart De Strooper, Tara L. Spires-Jones, Joris De Wit, Patrik Verstreken
Tau association with synaptic vesicles causes presynaptic dysfunction
published pages: 15295, ISSN: 2041-1723, DOI: 10.1038/ncomms15295
Nature Communications 8 2019-05-30
2017 Sarah-Maria Fendt, Patrik Verstreken
Neurons eat glutamate to stay alive
published pages: 863-865, ISSN: 0021-9525, DOI: 10.1083/jcb.201702003
The Journal of Cell Biology 216/4 2019-05-30
2016 Baptiste Fischer, Kevin Lüthy, Jone Paesmans, Charlotte De Koninck, Ine Maes, Jef Swerts, Sabine Kuenen, Valerie Uytterhoeven, Patrik Verstreken, Wim Versées
Skywalker-TBC1D24 has a lipid-binding pocket mutated in epilepsy and required for synaptic function
published pages: 965-973, ISSN: 1545-9993, DOI: 10.1038/nsmb.3297
Nature Structural & Molecular Biology 23/11 2019-05-30
2018 Jorge S. Valadas, Giovanni Esposito, Dirk Vandekerkhove, Katarzyna Miskiewicz, Liesbeth Deaulmerie, Susanna Raitano, Philip Seibler, Christine Klein, Patrik Verstreken
ER Lipid Defects in Neuropeptidergic Neurons Impair Sleep Patterns in Parkinson’s Disease
published pages: 1155-1169.e6, ISSN: 0896-6273, DOI: 10.1016/j.neuron.2018.05.022
Neuron 98/6 2019-05-30
2017 Roeland Vanhauwaert, Sabine Kuenen, Roy Masius, Adekunle Bademosi, Julia Manetsberger, Nils Schoovaerts, Laura Bounti, Serguei Gontcharenko, Jef Swerts, Sven Vilain, Marina Picillo, Paolo Barone, Shashini T Munshi, Femke MS de Vrij, Steven A Kushner, Natalia V Gounko, Wim Mandemakers, Vincenzo Bonifati, Frederic A Meunier, Sandra‐Fausia Soukup, Patrik Verstreken
The SAC1 domain in synaptojanin is required for autophagosome maturation at presynaptic terminals
published pages: 1392-1411, ISSN: 0261-4189, DOI: 10.15252/embj.201695773
The EMBO Journal 36/10 2019-05-30
2017 Melissa Vos, Ann Geens, Claudia Böhm, Liesbeth Deaulmerie, Jef Swerts, Matteo Rossi, Katleen Craessaerts, Elvira P. Leites, Philip Seibler, Aleksandar Rakovic, Thora Lohnau, Bart De Strooper, Sarah-Maria Fendt, Vanessa A. Morais, Christine Klein, Patrik Verstreken
Cardiolipin promotes electron transport between ubiquinone and complex I to rescue PINK1 deficiency
published pages: 695-708, ISSN: 0021-9525, DOI: 10.1083/jcb.201511044
The Journal of Cell Biology 216/3 2019-05-30
2016 Micheline Grillet, Beatriz Dominguez Gonzalez, Adria Sicart, Maria Pöttler, Ana Cascalho, Karolien Billion, Sergio Hernandez Diaz, Jef Swerts, Teresa V. Naismith, Natalia V. Gounko, Patrik Verstreken, Phyllis I. Hanson, Rose E. Goodchild
Torsins Are Essential Regulators of Cellular Lipid Metabolism
published pages: 235-247, ISSN: 1534-5807, DOI: 10.1016/j.devcel.2016.06.017
Developmental Cell 38/3 2019-05-30
2016 John D. Murdoch, Christine M. Rostosky, Sindhuja Gowrisankaran, Amandeep S. Arora, Sandra-Fausia Soukup, Ramon Vidal, Vincenzo Capece, Siona Freytag, Andre Fischer, Patrik Verstreken, Stefan Bonn, Nuno Raimundo, Ira Milosevic
Endophilin-A Deficiency Induces the Foxo3a-Fbxo32 Network in the Brain and Causes Dysregulation of Autophagy and the Ubiquitin-Proteasome System
published pages: 1071-1086, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2016.09.058
Cell Reports 17/4 2019-05-30
2018 Jorge S Valadas, Patrik Verstreken
p13 protects against Parkinson\'s disease
published pages: e45900, ISSN: 1469-221X, DOI: 10.15252/embr.201845900
EMBO reports 19/3 2019-05-30
2016 J. R. Slabbaert, S. Kuenen, J. Swerts, I. Maes, V. Uytterhoeven, J. Kasprowicz, A. C. Fernandes, R. Blust, P. Verstreken
Shawn, the Drosophila Homolog of SLC25A39/40, Is a Mitochondrial Carrier That Promotes Neuronal Survival
published pages: 1914-1929, ISSN: 0270-6474, DOI: 10.1523/JNEUROSCI.3432-15.2016
Journal of Neuroscience 36/6 2019-05-30
2018 Joseph McInnes, Keimpe Wierda, An Snellinx, Laura Bounti, Yu-Chun Wang, Ilie-Cosmin Stancu, Nuno Apóstolo, Kris Gevaert, Ilse Dewachter, Tara L. Spires-Jones, Bart De Strooper, Joris De Wit, Lujia Zhou, Patrik Verstreken
Synaptogyrin-3 Mediates Presynaptic Dysfunction Induced by Tau
published pages: 823-835.e8, ISSN: 0896-6273, DOI: 10.1016/j.neuron.2018.01.022
Neuron 97/4 2019-05-30
2017 Yu-Chun Wang, Elsa Lauwers, Patrik Verstreken
Presynaptic protein homeostasis and neuronal function
published pages: 38-46, ISSN: 0959-437X, DOI: 10.1016/j.gde.2017.01.015
Current Opinion in Genetics & Development 44 2019-05-30
2016 Sara Calafate, William Flavin, Patrik Verstreken, Diederik Moechars
Loss of Bin1 Promotes the Propagation of Tau Pathology
published pages: 931-940, ISSN: 2211-1247, DOI: 10.1016/j.celrep.2016.09.063
Cell Reports 17/4 2019-05-30
2016 Elsa Lauwers, Rose Goodchild, Patrik Verstreken
Membrane Lipids in Presynaptic Function and Disease
published pages: 11-25, ISSN: 0896-6273, DOI: 10.1016/j.neuron.2016.02.033
Neuron 90/1 2019-05-30
2017 Vinoy Vijayan, Patrik Verstreken
Autophagy in the presynaptic compartment in health and disease
published pages: 1895-1906, ISSN: 0021-9525, DOI: 10.1083/jcb.201611113
The Journal of Cell Biology 216/7 2019-05-30
2017 Sandra-Fausia Soukup, Patrik Verstreken
EndoA/Endophilin-A creates docking stations for autophagic proteins at synapses
published pages: 971-972, ISSN: 1554-8627, DOI: 10.1080/15548627.2017.1286440
Autophagy 13/5 2019-05-30
2018 Kristofer Davie, Jasper Janssens, Duygu Koldere, Maxime De Waegeneer, Uli Pech, Łukasz Kreft, Sara Aibar, Samira Makhzami, Valerie Christiaens, Carmen Bravo González-Blas, Suresh Poovathingal, Gert Hulselmans, Katina I. Spanier, Thomas Moerman, Bram Vanspauwen, Sarah Geurs, Thierry Voet, Jeroen Lammertyn, Bernard Thienpont, Sha Liu, Nikos Konstantinides, Mark Fiers, Patrik Verstreken, Stein Aerts
A Single-Cell Transcriptome Atlas of the Aging Drosophila Brain
published pages: , ISSN: 0092-8674, DOI: 10.1016/j.cell.2018.05.057
Cell 2019-05-30
2018 Ulrike Pech, Patrik Verstreken
α-Synuclein and Tau: Mitochondrial Kill Switches
published pages: 3-4, ISSN: 0896-6273, DOI: 10.1016/j.neuron.2017.12.024
Neuron 97/1 2019-05-30
2016 Wim Dejonghe, Sabine Kuenen, Evelien Mylle, Mina Vasileva, Olivier Keech, Corrado Viotti, Jef Swerts, Matyáš Fendrych, Fausto Andres Ortiz-Morea, Kiril Mishev, Simon Delang, Stefan Scholl, Xavier Zarza, Mareike Heilmann, Jiorgos Kourelis, Jaroslaw Kasprowicz, Le Son Long Nguyen, Andrzej Drozdzecki, Isabelle Van Houtte, Anna-Mária Szatmári, Mateusz Majda, Gary Baisa, Sebastian York Bednarek, Stéphanie Robert, Dominique Audenaert, Christa Testerink, Teun Munnik, Daniël Van Damme, Ingo Heilmann, Karin Schumacher, Johan Winne, Jiří Friml, Patrik Verstreken, Eugenia Russinova
Mitochondrial uncouplers inhibit clathrin-mediated endocytosis largely through cytoplasmic acidification
published pages: 11710, ISSN: 2041-1723, DOI: 10.1038/ncomms11710
Nature Communications 7 2019-05-30
2017 Adekunle T. Bademosi, Elsa Lauwers, Pranesh Padmanabhan, Lorenzo Odierna, Ye Jin Chai, Andreas Papadopulos, Geoffrey J. Goodhill, Patrik Verstreken, Bruno van Swinderen, Frédéric A. Meunier
In vivo single-molecule imaging of syntaxin1A reveals polyphosphoinositide- and activity-dependent trapping in presynaptic nanoclusters
published pages: 13660, ISSN: 2041-1723, DOI: 10.1038/ncomms13660
Nature Communications 8 2019-05-30
2018 Lujia Zhou, Patrik Verstreken
Reprogramming neurodegeneration in the big data era
published pages: 167-173, ISSN: 0959-4388, DOI: 10.1016/j.conb.2017.12.015
Current Opinion in Neurobiology 48 2019-05-30

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