TY - JOUR TI - Selective agonist of TRPML2 reveals direct role in chemokine release from innate immune cells AU - Plesch, Eva AU - Chen, Cheng-Chang AU - Butz, Elisabeth AU - Scotto Rosato, Anna AU - Krogsaeter, Einar K AU - Yinan, Hua AU - Bartel, Karin AU - Keller, Marco AU - Robaa, Dina AU - Teupser, Daniel AU - Holdt, Lesca M AU - Vollmar, Angelika M AU - Sippl, Wolfgang AU - Puertollano, Rosa AU - Medina, Diego AU - Biel, Martin AU - Wahl-Schott, Christian AU - Bracher, Franz AU - Grimm, Christian A2 - Dustin, Michael L A2 - Aldrich, Richard VL - 7 PY - 2018 DA - 2018/11/27 SP - e39720 C1 - eLife 2018;7:e39720 DO - 10.7554/eLife.39720 UR - https://doi.org/10.7554/eLife.39720 AB - Cytokines and chemokines are produced and secreted by a broad range of immune cells including macrophages. Remarkably, little is known about how these inflammatory mediators are released from the various immune cells. Here, the endolysosomal cation channel TRPML2 is shown to play a direct role in chemokine trafficking and secretion from murine macrophages. To demonstrate acute and direct involvement of TRPML2 in these processes, the first isoform-selective TRPML2 channel agonist was generated, ML2-SA1. ML2-SA1 was not only found to directly stimulate release of the chemokine CCL2 from macrophages but also to stimulate macrophage migration, thus mimicking CCL2 function. Endogenous TRPML2 is expressed in early/recycling endosomes as demonstrated by endolysosomal patch-clamp experimentation and ML2-SA1 promotes trafficking through early/recycling endosomes, suggesting CCL2 being transported and secreted via this pathway. These data provide a direct link between TRPML2 activation, CCL2 release and stimulation of macrophage migration in the innate immune response. KW - TRPML2 KW - TRPML KW - lysosome KW - CCL2 KW - macrophage KW - Mcoln2 JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -