Identification and functional characterization of chemokine receptor interacting proteins

• Applicant: Professor Dr. Martin Oppermann
• Subject Area: Biochemistry
• Term: from 2009 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 124047234

Chemokine receptors CCR5 and CXCR4 are G protein-coupled receptors (GPCR) which fulfill important functions in the immune system and also act as HIV co-receptors for viral entry into target cells. Ligand stimulation activates similar signaling pathways downstream of CCR5/CXCR4 and induces receptor internalization from the plasma membrane into the cell, yet the intracellular fates of both receptors differ. While CCR5 rapidly recycles back to the cell surface, a significant fraction of CXCR4 is targeted for lysosomal degradation. The receptor carboxyl-terminal domains contain sites which target receptors to different subcellular compartments, but the corresponding intracellular sorting proteins are not known. This project aims at identification and functional characterization of intracellular proteins which interact with cytoplasmic domains of CCR5 or CXCR4 by affinity purification of receptor-associated multiprotein complexes in combination with mass spectrometry. Proteins which interact with CCR5 vs. CXCR4 in their non-/activated states will be identified and their functions for receptor trafficking to and from the plasma membrane or for fine-tuning the cellular response to chemokine stimulation will be investigated.

• DFG Programme: Research Grants