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Chemokine receptors are GPCRs that regulate chemotactic migration of a wide variety of cells including immune and cancer cells. Most chemokine receptors contain features associated with the ability to stimulate G proteins during β-arrestin-mediated internalization into endosomes. As endosomal signaling of certain non-GPCR receptors plays a major role in cell migration, we chose to investigate the potential role of endosomal chemokine receptor signaling on mechanisms governing this function. Applying cell biological approaches and spatiotemporal-resolved proteome profiling, we demonstrate that the model chemokine receptor CCR7 recruits G protein and β-arrestin simultaneously upon chemokine stimulation enabling internalized receptors to activate G protein from endosomes. Furthermore, endosomal CCR7 uniquely enriches specific Rho-GTPase regulators as compared to plasma membrane CCR7, which is associated with enhanced activity of Rho-GTPase Rac1. As Rac1 drives the formation of membrane protrusions during chemotaxis, our findings suggest an important integrated function of endosomal chemokine receptor signaling in cell migration.

The aim of this study was to assess the alkaline phosphatase activity of representative cheeses made from pasteurised milk in the United Kingdom. The results generated will contribute to similar data from other EU Member States to assess the efficacy of setting a legal standard of a maximum of 10 mU/g for such cheeses. The study indicated that UK cheeses had a probability of 97.68% of meeting such a standard. This is however probably an underestimate as one cheese was sprayed with honey which may harbour yeasts, some species of which produce the alkaline phosphatase enzyme, which may have skewed the statistical analysis.