P2Y11: The CD4 T cell mitochondrial shepherd

[摘要] T cells are activated after engagement of their TCRs with cognateantigen presented by APCs, with the aid of costimulatory signals.These signals, which irradiate from a multiprotein structure formedby clusters of TCR, CD3, and costimulatory receptors such as CD28and anchor molecules (e.g., LFA-1) called immunologic synapse (IS),serve to amplify the intracellular cascades, leading to changes in protein phosphorylation and, ultimately, to module gene expression andprotein synthesis.1 Purinergic signaling, that is, engagement of extracellular nucleotides by specific receptors, has been shown to promote CD4 T cell migration, proliferation, and subset differentiation.2Quickly after activation, the extracellular ATP (eATP) receptor P2X4and Panx1 (a hemichannel that promotes ATP release to the extracellular milieu) concentrate in the IS and promote stable, continuous interaction APCs.3 Among the events leading to T cell activation,the rearrangement of mitochondria in the cytoplasm is a fundamental step, where an accumulation of mitochondria around the IS provides a source of ATP needed for the chain reactions happening atthat intracellular region. This includes ATP release via Panx1 and subsequent stimulation of P2X4.3 However, the intracellular mechanismsleading to the redistribution of mitochondria at the IS are poorly understood. In this issue of The Journal of Leukocyte Biology, Ledderose et al.4addressed this question and described that the eATP receptor P2Y11plays a fundamental role in promoting the migration of mitochondriatoward the IS.

[学科分类] 生理学