Objective
We have recently reported on a novel mode of modulation of neuronal transmission at the glutamatergic junction. This signaling pathway involves lysophosphatidic acid (LPA) acting via presynaptic LPA2 receptors. This is in turn controlled by a molecule which we named plasticity related gene-1 (PRG-1, Bräuer et al., Nat Neurosci 2003) from the postsynaptic side (Trimbuch et al., Cell 2009). PRG-1 is a brain-specific membrane protein related to lipid phosphate phosphatases (LPPs) with a selective expression in neurons (Geist et al., CMLS 2011). We detected an important role of LPA-synthesizing pathways in bioactive signaling at the synapse acting via ATX and etablished nano-particles as LPA-biosensor using the characteristic spectral shift allowing detection in 2-photon imaging. We provide insights into the oligomeric assembly of PRG-1 in the membrane and assessed LPA-binding, uptake and intracellular interaction partners of the molecule. Animals lacking one PRG-1 allele exhibit a broad spectrum of behavioral pathology indicative of altered brain network function and psychiatric disorders. These changes are already present in animals lacking only 50% of PRG-1. A point mutation at R345T which appears to result in loss-of-function when re-expressed in the mouse was found in 5925 healthy individuals with a heterozygous frequency of approximately 0.86% (about 4.500.000 European citizens). Individuals carrying this loss-of-function mutation revealed functional alterations of sensory gating involved in psychiatric disorders. We plan to continue our studies on (1) synthesis and action of LPA, (2) molecular function of PRG-1 in bioactive lipid signaling, and (3) the role of PRG-1 signaling in brain network function and psychiatric disorders. Characterization of the molecular basis of this novel modulatory signaling pathway and its role in brain network function will be important for our understanding of its role in health and disease.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: https://op.europa.eu/en/web/eu-vocabularies/euroscivoc.
- medical and health sciences clinical medicine psychiatry
- natural sciences biological sciences biochemistry biomolecules lipids
- natural sciences biological sciences genetics mutation
- medical and health sciences basic medicine pathology
- engineering and technology nanotechnology nano-materials
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Programme(s)
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Multi-annual funding programmes that define the EU’s priorities for research and innovation.
Topic(s)
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Calls for proposals are divided into topics. A topic defines a specific subject or area for which applicants can submit proposals. The description of a topic comprises its specific scope and the expected impact of the funded project.
Call for proposal
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Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
ERC-2012-ADG_20120314
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Funding Scheme
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Funding scheme (or “Type of Action”) inside a programme with common features. It specifies: the scope of what is funded; the reimbursement rate; specific evaluation criteria to qualify for funding; and the use of simplified forms of costs like lump sums.
Host institution
55131 Mainz
Germany
The total costs incurred by this organisation to participate in the project, including direct and indirect costs. This amount is a subset of the overall project budget.