Objective
The dopamine transporter (DAT) belongs to the family of Na+/Cl- dependent neurotransmitter transporters and is responsible for rapid termination of dopaminergic signaling by mediating reuptake of dopamine (DA) from the synaptic cleft. The DAT is target for widely abused psychostimulants, such as amphetamine and cocaine, as well as modification in DAT activity has been associated with severe brain disorders like Parkinson’s disease, schizophrenia and attention deficit hyperactivity disorder (ADHD). An increasing number of proteins have been identified as interaction partners of the DAT but the functional implications of the interactions are poorly understood. Here we propose to investigate the molecular significance of the interaction between DAT and the PDZ domain protein PICK1. Based on a series of preliminary data we propose that binding of PICK1 via its PDZ domain to the DAT C-terminus operate to regulate uncoupled DAT mediated currents. Notably, these currents are likely to modulate the excitability of dopaminergic neurons and thereby the overall activity of the dopamine system. We hypothesize that PICK1 mediated regulation of these currents either involves enhanced DAT phosphorylation due to PICK1 mediated recruitment of protein kinase Ca or modulation of intramolecular interactions in the transporter molecule. We will test our hypotheses by employing an interdisciplinary strategy that combines the expertise of the applicants with those of the host laboratory and involves a broad spectrum of methods including patch clamp measurements, bioimaging and molecular biological procedures. We expect that the project will lead to significant improvement of our understanding of DAT regulation and thereby provide an important framework for future discovery of novel therapeutic strategies against diseases characterized by dopaminergic dysfunction.
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: The European Science Vocabulary.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques. See: The European Science Vocabulary.
- natural sciences biological sciences biochemistry biomolecules proteins
- medical and health sciences basic medicine neurology parkinson
- medical and health sciences clinical medicine psychiatry schizophrenia
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Keywords
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
Project’s keywords as indicated by the project coordinator. Not to be confused with the EuroSciVoc taxonomy (Fields of science)
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
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
Procedure for inviting applicants to submit project proposals, with the aim of receiving EU funding.
FP7-PEOPLE-2007-2-1-IEF
See other projects for this call
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.
Coordinator
1165 KOBENHAVN
Denmark
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.