Functional proteomics of native CXCR4 and ACKR3-operated signalling

Early stage researcher 9 (ESR9) project
Supervision: Prof. Dr. Philippe Marin, Dr. Séverine Chaumont-Dubel
Host: CNRS 

I – Project proposal:

Aim:

  1. Characterization of ACKR3 interactome in HA-ACKR3 knock-in mice
  2. Characterization of phosphoproteomes under the control of CXCR4, ACKR3 and CXCR4/ACKR3 heteromers

Methodology:

    1. The ACKR3 interactome will be investigated using an AP-MS (affinity purification coupled to mass spectrometry) strategy. HA-tagged ACKR3 will be immunoprecipitated from knock-in mice tissues using immobilized anti-HA antibody and immunoprecipitated proteins will be identified by LC-MS/MS. Some potentially interesting partners will then be functionally validated in vitro, in cultured cells, and in vivo.
    2. The entire phosphoproteome under the control of ACKR3 and ACKR3/CXCR4 heteromers will be analysed in cells and tissues using a quantitative phosphoproteomics approach combining phosphorylated peptide enrichment on TiO2 beads and their identification by LC-MS/MS. Some key phosphorylation events will be functionally validated by antibody-based strategies and site-directed mutagenesis.

Planned secondments:

Universitätsklinikum JENA (Dr. Ralf Stumm’s laboratory)

Universidad Autónoma de Madrid, Department of Molecular Biology  

 

II – Requirement candidate:

Required diploma: MSc in molecular/biochemical Life Sciences, pharmaceutical sciences or related Life-Science degree.

Required expertise: biochemistry, pharmacology, molecular and cell biology, cell cultures.

Recommended expertise: notions in proteomics and mass spectrometry, knowledge of protein databases, notions in bioinformatics

Key publications:

  1. Murat S, Bigot M, Chapron J, König GM, Kostenis E, Battaglia G, Nicoletti F, Bourinet E, Bockaert J, Marin P*, Vandermoere F*. 5-HT(2A) receptor-dependent phosphorylation of mGlu(2) receptor at Serine 843 promotes mGlu(2) receptor-operated G(i/o) signaling. Mol Psychiatry. 2018 Jun 1. doi: 10.1038/s41380-018-0069-6.
  2. Cassier E, Gallay N, Bourquard T, Claeysen S, Bockaert J, Crépieux P, Poupon A, Reiter E, Marin P*, Vandermoere F*. (2017) Phosphorylation of β-arrestin 2 at Thr383 by MEK underlies β-arrestin-dependent activation of Erk1/2 by GPCRs. eLife 10.7554/eLife.23777.
  3. Deraredj Nadim W., Chaumont-Dubel S., Madouri F., Cobret L., De Tauzia1 M.L., Zajdel P., Bénédetti H., Marin P. & Morisset-Lopez S. (2016) A physical interaction between neurofibromin and serotonin 5-HT6 receptor promotes receptor constitutive activity. Proc Natl Acad Sci USA. 113(43):12310-12315.
  4. Duhr F, Déléris P, Raynaud F, Séveno M, Morisset-Lopez S, Mannoury la Cour C, Millan MJ, Bockaert J, Marin P*, Chaumont-Dubel S*. (2014) Cdk5 induces constitutive activation of 5-HT6 receptors to promote neurite growth. Nat Chem Biol. 10(7):590-7. (PMID: 24880860). News & Views: Seo J, Tsai LH. Neuronal differentiation: 5-HT6R can do it alone. Nat Chem Biol. 2014 Jul;10(7):488-9.
  5. Meffre J, Chaumont-Dubel S, Mannoury la Cour C, Loiseau F, Watson DJ, Dekeyne  A, Séveno M, Rivet JM, Gaven F, Déléris P, Hervé D, Fone KC, Bockaert J, Millan MJ, Marin P. (2012) 5-HT(6) receptor recruitment of mTOR as a mechanism for perturbed cognition in schizophrenia. EMBO Mol Med. 4(10):1043-56.

For more information:
Prof. Dr. Philippe Marin – philippe.marin@igf.cnrs.fr

Dr. Séverine Chaumont-Dubel – severine.chaumont-dubel@igf.cnrs.fr

 

Application:

Please send your application to Philippe.marin@igf.cnrs.fr

Include in heading – ONCORNET2.0 application + ESR#

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Contact details

Please contact us at:
info@oncornet.eu

ONCORNET Coordinator
VU University Amsterdam
The Netherlands