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SynDegrade SIGNED

The Role of Local Protein Degradation in Neurotransmitter Release and Homeostatic Plasticity

Total Cost €

EC-Contrib. €

Partnership

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Outcomes and
results

SynDegrade project word cloud

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

epilepsy employing decades local poses neural realized analyze signaling tightly henceforth stabilize neurons lives degradation biophysical description while synapse hours synapses genes abundance homeostatic composition mechanisms uncontrolled chemical synaptic presynaptic neurological poorly ideally combination electrophysiological question ubiquitin cns plasticity drosophila underlying probes translated weeks classes live regulating nervous learning proteostasis stable unknown dependent pathology phenomenon regulation function acutely genetics mutants encoded plastic physiology migraine molecular levels release largely proteins modulation mammalian proteasome diseases site ups genetically suited unravel dissect linked neurotransmitter perturb systematically transmission half maintained protein

Project "SynDegrade" data sheet

The following table provides information about the project.

Coordinator	UNIVERSITAT ZURICH Organization address address: RAMISTRASSE 71 city: Zürich postcode: 8006 website: http://www.unizh.ch 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	Switzerland [CH]
Total cost	1˙489˙340 €
EC max contribution	1˙489˙340 € (100%)
Programme	1. H2020-EU.1.1. (EXCELLENT SCIENCE - European Research Council (ERC))
Code Call	ERC-2015-STG
Funding Scheme	ERC-STG
Starting year	2016
Duration (year-month-day)	from 2016-05-01 to 2021-04-30

Partnership

Take a look of project's partnership.

#	participants	country	role	EC contrib. [€]
1	UNIVERSITAT ZURICH UNIVERSITAT ZURICH Organization address address: RAMISTRASSE 71 city: Zürich postcode: 8006 website: http://www.unizh.ch contact info title: n.a. name: n.a. surname: n.a. function: n.a. email: n.a. telephone: n.a. fax: n.a.	CH (Zürich)	coordinator	1˙489˙340.00

Map

Project objective

While many neurons live for decades, the proteins that determine neural function have half-lives of hours to weeks. On the one hand, this allows for plastic changes during development and learning. On the other hand, this poses the question of how stable neural function can be achieved and maintained at all. Several neurological diseases, such as epilepsy or migraine, have been linked to uncontrolled neural function. However, the molecular mechanisms that stabilize nervous system function are poorly understood. The major site of regulation of neural activity is the chemical synapse. Synaptic function is tightly linked to the specific composition and abundance of proteins at synapses. However, the molecular pathways underlying the homeostatic control of protein levels at synapses, henceforth called synaptic proteostasis, are largely unknown.

The main objective of this proposal is to unravel the molecular signaling systems underlying synaptic proteostasis through local protein degradation, and its role in regulating a key step in synaptic transmission: neurotransmitter release. We propose to systematically analyze Ubiquitin Proteasome System (UPS)-dependent modulation of synaptic transmission in mutants of all major classes of synaptic genes, with a focus on homeostatic plasticity genes. This will be realized by employing a unique combination of forward genetics and electrophysiological analysis of synaptic transmission in Drosophila. Novel genetically-encoded probes will be used and developed to study synaptic transmission and protein degradation, and to acutely perturb protein function. Finally, this new information will be translated into the mammalian CNS by studying UPS-dependent modulation of release at a CNS synapse that allows for a detailed biophysical description of this phenomenon. Together, this approach should be ideally suited to dissect the molecular signaling systems underlying presynaptic proteostasis, and its role in neural physiology and pathology.

Publications

List of publications.
year	authors and title	journal	last update
2019	Igor Delvendahl, Martin MÃ¼ller Homeostatic plasticityâ€”a presynaptic perspective published pages: 155-162, ISSN: 0959-4388, DOI: 10.1016/j.conb.2018.10.003	Current Opinion in Neurobiology 54	2019-02-11

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The information about "SYNDEGRADE" are provided by the European Opendata Portal: CORDIS opendata.