Authors:

Aashka Trivedi

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About Paper:

G-protein-coupled chemokine receptors facilitate the migration of leukocytes to sites of inflammation, infection, or injury. Excessive activation of leukocytes is observed in inflammatory diseases and many forms of cancer in an aggressive immune response. Chemokine receptors are thus an important target for therapeutic development. Our previous research has found that chemokine receptors form oligomeric assemblies at high cell surface density, leading the receptors to allosterically modulate their structure, remodel ligand binding sites, and enhance G-protein activation. It has been demonstrated that there is an increased presentation of chemokine receptors is observed on the cell surface in oncogenic cells as well as in the cells of patients with neurological and neuroinflammatory diseases, resulting in the inflammatory response. Proteomics and lipidomic analysis reveal unique signaling pathways and receptor-associated lipids between monomeric and trimeric CXCR-4, indicating a unique function of these oligomeric assemblies. Data shows increased levels of proteins involved in the oxidative stress response in the trimeric samples, indicating a probable role of trimeric CXCR-4 _in managing oxidative stress and responding to reactive oxygen species. We also find significant difference in ether-linked CXCR-4 associated lipids, suggesting a role in the progression of metabolic disease. This study aims to elucidate major differences between oligomeric assemblies and their potential role in pathogenesis. We anticipate these findings will assist in the development of pharmaceuticals and therapies for the many diseases in which CXCR-4 is implicated. SOS HOSS OOO HOH OOH OOS HS HOH OOOOH EH OCOHOCCOCOOCHEOCOCEO PDIDDDIPSDIDDIDIDD IDI DIDIDS SDDDDDHDHHOHDIDGDISSO

Source:

University of Illinois Chicago

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Co-authors:

Aashka Trivedi