Summary
G protein-coupled receptor (GPCR) are membrane proteins targeted by around 30 % of all marketed drugs. GPCR internalization is a mechanism that tunes the cell surface versus intracellular receptor ratio, a parameter that plays an essentiG protein-coupled receptor (GPCR) internalization is a mechanism involved in the tuning of cell surface versus intracellular receptor ratio, a parameter that plays an essential role in controlling receptor physiological responses. This process is very well described for many GPCRs but surprisingly not for metabotropic glutamate receptors, mandatory dimeric GPCRs that are ubiquitously expressed in the brain to regulate neuronal transmission. Deciphering which are the internalization pathways related to mGlus emerge as a strategy for the regulation of their response to not only drugs but also endogenous neurotransmitters.
I propose to examine the internalization profiles of mGlus in brain cells and to unravel the structural and molecular mechanisms involved in the process. I will use a biophysical technique optimized by the host team that allows the real-time and quantitative measurement of receptor internalization in both recombinant cells and brain cells, in combination with a microscopy approach that will complement the analysis. On top of that, I will use nanomolar range affinity nanobodies, single domain antibodies that have already been developed by the host team as a tool for ultimately elucidate which are the internalization profile of mGlus in brain cells.
As a consequence of this project, the internalization profile of mGlus in neurons and astrocytes, and the cell machinery responsible for this process will be clarified for the first time. This knowledge will allow the fine-tuning of mGlus localization in the cell, as well as the validation of the nanobodies as a tool for studying endogenous mGlus. These outcomes will upgrade the current resources that the scientific community has to modulate mGlu receptor-mediated responses.
I propose to examine the internalization profiles of mGlus in brain cells and to unravel the structural and molecular mechanisms involved in the process. I will use a biophysical technique optimized by the host team that allows the real-time and quantitative measurement of receptor internalization in both recombinant cells and brain cells, in combination with a microscopy approach that will complement the analysis. On top of that, I will use nanomolar range affinity nanobodies, single domain antibodies that have already been developed by the host team as a tool for ultimately elucidate which are the internalization profile of mGlus in brain cells.
As a consequence of this project, the internalization profile of mGlus in neurons and astrocytes, and the cell machinery responsible for this process will be clarified for the first time. This knowledge will allow the fine-tuning of mGlus localization in the cell, as well as the validation of the nanobodies as a tool for studying endogenous mGlus. These outcomes will upgrade the current resources that the scientific community has to modulate mGlu receptor-mediated responses.
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| Web resources: | https://cordis.europa.eu/project/id/101065171 |
| Start date: | 01-09-2023 |
| End date: | 31-08-2025 |
| Total budget - Public funding: | - 195 914,00 Euro |
Cordis data
Original description
G protein-coupled receptor (GPCR) are membrane proteins targeted by around 30 % of all marketed drugs. GPCR internalization is a mechanism that tunes the cell surface versus intracellular receptor ratio, a parameter that plays an essentiG protein-coupled receptor (GPCR) internalization is a mechanism involved in the tuning of cell surface versus intracellular receptor ratio, a parameter that plays an essential role in controlling receptor physiological responses. This process is very well described for many GPCRs but surprisingly not for metabotropic glutamate receptors, mandatory dimeric GPCRs that are ubiquitously expressed in the brain to regulate neuronal transmission. Deciphering which are the internalization pathways related to mGlus emerge as a strategy for the regulation of their response to not only drugs but also endogenous neurotransmitters.I propose to examine the internalization profiles of mGlus in brain cells and to unravel the structural and molecular mechanisms involved in the process. I will use a biophysical technique optimized by the host team that allows the real-time and quantitative measurement of receptor internalization in both recombinant cells and brain cells, in combination with a microscopy approach that will complement the analysis. On top of that, I will use nanomolar range affinity nanobodies, single domain antibodies that have already been developed by the host team as a tool for ultimately elucidate which are the internalization profile of mGlus in brain cells.
As a consequence of this project, the internalization profile of mGlus in neurons and astrocytes, and the cell machinery responsible for this process will be clarified for the first time. This knowledge will allow the fine-tuning of mGlus localization in the cell, as well as the validation of the nanobodies as a tool for studying endogenous mGlus. These outcomes will upgrade the current resources that the scientific community has to modulate mGlu receptor-mediated responses.
Status
SIGNEDCall topic
HORIZON-MSCA-2021-PF-01-01Update Date
09-02-2023
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