FP7Reintegration grant2008–2012

ADENOSINE-RECEPTOR · Identification of the protein interactome of the A2A-adenosine receptor

FP7 — People (Marie Curie Actions)

Duration
2008-09-01 → 2012-08-31
EU contribution
€100,000
Participants
1
Scheme
MC-IRG

Lines connect the coordinator with its partners.

Results in brief

Identification of the protein interactome of the A2A-adenosine receptor

Proteins can be viewed like social actors, they form many different complexes with each other. A receptor that resides on the cell surface membrane of a given cell is actually synthesized at a very different site, namley in the endoplasmic reticulum. From this site of its birth, it has to travel to the surface. Because G protein-coupled receptors are membrane proteins, they cannot simply travel through the aqueous milieu of the cytosol. They must stay embedded in a membrane. They are The project aimed at understanding which

Data: CORDIS, © European Union

Project objective

The A2A-adenosine receptor is a Gs-coupled receptor, which has several unique structural and functional characteristics. Recently, the C-terminus of the receptor has been appreciated as a binding site for several “accessory” proteins, of which only half a dozen are established. It is clear that (i) this list cannot be exhaustive and (ii) that all these proteins cannot bind simultaneously to the receptor. The challenging, but very important task is to document which of all these interactions do occur in the living organisms. Here we propose to meet this challenge by characterizing the interactome of the A2A-receptor by using a two-step proteomics approach; i.e., the receptor will first be expressed in tagged versions in cells, which can be differentiated into neurons. This will allow for optimization of the conditions and for an initial survey of interaction partners; subsequently, we intend to generate mice, in which the receptor has been engineered to afford the isolation of receptor-complexes from native tissues, in particular the striatum. To the best of our knowledge, the proposed strategy has not yet been pursued with other GPCRs. Thus, if successful, it may set a precedent and provide the proof-of-principle for the entire family of GPCRs. At the very least, the current approach provides the ‘acid test’ for all purported interactors of the A2A-receptor.

Original text from CORDIS.

Participants

  • MEDIZINISCHE UNIVERSITAET WIEN · WienCoordinatorAustria

Links

Data: CORDIS, © European Union