The purinergic receptor P2Y11 choreographs the polarization, mitochondrial metabolism, and migration of T lymphocytes

• DOI: 10.1126/scisignal.aba3300
• Publication Date: 2020-09-29T23:12:02Z
• Authors: Carola Ledderose; Sophie Bromberger; Christian J. Slub...; Koichiro Sueyoshi; Dilan Aytan; Yong Shen; Wolfgang G. Junger
• Keywords: Purinergic Signalling

T cells must migrate to encounter antigen-presenting and perform their roles in host defense. Here, we found that autocrine stimulation of the purinergic receptor P2Y11 regulates migration human CD4 cells. receptors redistributed from front back polarized where they triggered intracellular cAMP/PKA signals attenuated mitochondrial metabolism at back. The absence resulted hotspots localized ATP production stimulated P2X4 receptors, Ca2+ influx, pseudopod protrusion front. This regulatory function depended on subcellular redistribution by cellular release was perturbed indiscriminate global stimulation. We conclude excessive extracellular ATP-such as response inflammation, sepsis, cancer-disrupts this feedback mechanism, which results defective cell migration, impaired function, loss immune