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Séminaire impromptu - Sandra Fausia SoukupSynaptic autophagy: a new perspective in Parkinson disease / Candidate à une chaire Bordeaux Neurocampus

Abstract :

 Synapses are the communication center of the neurons but they are especially vulnerable,
since they are located far away from the soma and undergo highly active periods during neuronal communication that can lead to the accumulation of dysfunctional proteins. To ensure synaptic transmission, local synapse specific mechanism take place to cope with proteopathic stress and to restore synaptic homeostasis. Interestingly accumulating evidence places synaptic dysfunction prior to neuronal demise and not surprisingly a rising number of synaptic genes show mutations that cause or influence Parkinson’s disease. Understanding how presynaptic compartments turnover proteins might be crucial to decipher molecular mechanism of the early onset of Parkinson’s disease and potentially provide valuable knowledge to develop “early” biomarkers and specific drugs before irreversible synaptic decay has occurred. I will introduce some unique characteristic of synaptic autophagy, highlight how the synaptic proteins Endophilin-A and Synaptojanin control autophagy and elaborate their role in maintaining synaptic homeostasis and preventing neurodegeneration.

Selected publications

Vanhauwaert R., Kuenen S., Masius R., Bademosi A., Manetsberger J., Schoovaerts N., Bounti L., Gontcharenko S., Swerts J., Vilain S., Picillo M., Barone P., Munshi S., de Vrij F., Kushner S., Gunko N., Mandemakers W., Bonifati V., Meunier F., Soukup S., Verstreken P. (2017). The SAC1 domain in synaptojanin is required for autophagosome maturation at presynaptic terminals. EMBO Journal, 36 (10), e201695773, 1392-1411.

Soukup S., Verstreken P. (2017). EndoA/Endophilin-A creates docking stations for autophagic proteins at synapses. Autophagy, 13 (5), 10.1080/15548627.2017.1286440, 971-972.

Murdoch J., Rostosky C., Gowrisankaran S., Arora A., Soukup S., Vidal R., Capece V., Freytag S., Fischer A., Verstreken P., Bonn S., Raimundo N., Milosevic I. (2016). Endophilin-A Deficiency Induces the Foxo3a-Fbxo32 Network in the Brain and Causes Dysregulation of Autophagy and the Ubiquitin-Proteasome System. Cell Reports, 17 (4), 1071-1086.

Soukup S., Kuenen S., Vanhauwaert R., Manetsberger J., Hernandez Diaz S., Swerts J., Schoovaerts N., Vilain S., Gunko N., Vints K., Geens A., De Strooper B., Verstreken P. (2016). A LRRK2-Dependent EndophilinA Phosphoswitch Is Critical for Macroautophagy at Presynaptic Terminals. Neuron, 92 (4), S0896-6273(16)30638-9, 829-844.

Soukup S., Verstreken P. (2014). PIWIL1 protein power targets tau therapy. Nature Neuroscience, 17 (3), 10.1038/nn.3659, 334-5.

Vilain S., Vanhauwaert R., Maes I., Schoovaerts N., Zhou L., Soukup S., Cruz Carvalho da Cunha R., Lauwers E., Fiers M., Verstreken P. (2014). Fast and efficient Drosophila melanogaster gene knock-ins using MiMIC transposons. G3-Genes Genomes Genetics, 4 (12), 2381-2387.


Scientific focus :

Msc Biology, Albert Ludwig University Freiburg, Germany
Thesis advisor: Prof. Dr. Karl-Friedrich Fischbach
Unraveling axon guidance cues of the Robo-Slit- System in the development of the
optic lobe in Drosophila melanogaster

PhD in Biology, CIC BioGUNE/ University of the Basque Country, Spain
Thesis advisor: Dr. David Gubb
Understanding the innate immunity role in host-pathogens interactions and
disease: I characterized the role of the Drosophila podocyte-like cells in the uptake of
protease/serpin complexes by the receptor LpR1, a member of the low density lipid
receptor family (PMID: 19557185). Relevance: In humans, failing to uptake
protease/serpin complexes lead to the formation of insoluble polymers and disease.

Post Doctoral Training
Max Plank Institute for Cell Biology and Genetics (MPI-CBG), Dresden, Germany
Supervisor: Prof. Dr. Elisabeth Knust
Deciphering the impact of trans-synaptic signaling in retinal degeneration: I
revealed that DLin-7 forms a postsynaptic tripartite complex with CASK and DLGS97 and
that this complex controls presynaptic homeostasis in photoreceptors (PMID: 23850283).
Relevance: This mechanism is necessary to prevent retinal degeneration.

VIB Center for Brain & Disease Research/ KU Leuven, Department of Neurosciences,
Leuven, Belgium
Supervisor: Prof. Dr. Patrik Verstreken
Decoding the molecular mechanism of synaptic autophagy and its implication in
Parkinson’s disease:
I showed that LRRK2 dependent phosphorylation of Endophilin-A, a synapse specific
protein, promotes synaptic autophagy by creating docking sites for autophagic factors like
Atg3 (PMID: 27720484).
Moreover, we revealed that the Parkinson causative mutation R258Q in Synaptojanin, a
binding partner of Endophilin-A, prevents autophagosomal maturation in flies and in
human patient neurons derived from iPSCs (PMID: 28331029, corresponding author).
Relevance: Defects in synaptic autophagy might be a common pathway in
neurodegenerative diseases. These works open new avenues for understanding how
neurodegeneration starts before pathological and/or clinical signs appear.

Other Activities
To promote public awareness about Parkinson research in Leuven, I participated in the event “Patients meet Scientists”. Furthermore, I am organizing in our department the initiative “Woman in Scienc