@article{22371,
  abstract     = {Amoeboid cell migration is key to efficient T cell immunity. Spatial polarization of organelles within cells, including endo-lysosomes, is a prerequisite of migration. However, how ultrastructural polarization is linked to the signaling requirements governing T cell migration remains unknown. Here we show that signaling molecules generated by endo-lysosome-localized kinases regulate velocity of amoeboid migration. Specifically, imaging of T cells identifies accumulation of endo-lysosomes decorated with the lipid kinases VPS34–PIKfyve at the uropod of polarized cells. Activity of VPS34 and PIKfyve regulates speed, but not directedness, of migrating T cells. Mechanistically, PI(3,5)P2 generated by the sequential action of VPS34 and PIKfyve, mediates Ca2+ efflux from lysosomes via the mucolipin TRP cation channel 1 (TRPML1), thus controlling activity of myosin IIA and hence the generation of propulsive force through retrograde actin flow. The VPS34–PIKfyve kinases also regulate velocity of myeloid cells, as well as of the amoeba Dictyostelium discoideum – establishing the axis as an evolutionarily conserved speed control system of amoeboid cell migration.},
  author       = {Dehio, Philippe G and Michard, Céline and Yam-Puc, Juan Carlos and Martí I Líndez, Adrià Arnau and Jandke, Anett and Unterstab, Gunhild and Fabre, Lucien and Sauteur, Loïc and Artinger, Marc and Legler, Daniel F. and Sixt, Michael K and Schaefer, Thorsten and Wymann, Matthias P. and Okkenhaug, Klaus and Soldati, Thierry and Mehling, Matthias and Hess, Christoph},
  issn         = {1469-3178},
  journal      = {EMBO Reports},
  publisher    = {Springer Nature},
  title        = {{A conserved VPS34-PIKfyve-TRPML1-myosin II axis regulates the speed of amoeboid cell migration}},
  doi          = {10.1038/s44319-026-00861-x},
  year         = {2026},
}

@article{672,
  abstract     = {Trafficking cells frequently transmigrate through epithelial and endothelial monolayers. How monolayers cooperate with the penetrating cells to support their transit is poorly understood. We studied dendritic cell (DC) entry into lymphatic capillaries as a model system for transendothelial migration. We find that the chemokine CCL21, which is the decisive guidance cue for intravasation, mainly localizes in the trans-Golgi network and intracellular vesicles of lymphatic endothelial cells. Upon DC transmigration, these Golgi deposits disperse and CCL21 becomes extracellularly enriched at the sites of endothelial cell-cell junctions. When we reconstitute the transmigration process in vitro, we find that secretion of CCL21-positive vesicles is triggered by a DC contact-induced calcium signal, and selective calcium chelation in lymphatic endothelium attenuates transmigration. Altogether, our data demonstrate a chemokine-mediated feedback between DCs and lymphatic endothelium, which facilitates transendothelial migration.},
  author       = {Vaahtomeri, Kari and Brown, Markus and Hauschild, Robert and De Vries, Ingrid and Leithner, Alexander F and Mehling, Matthias and Kaufmann, Walter and Sixt, Michael K},
  issn         = {2211-1247},
  journal      = {Cell Reports},
  number       = {5},
  pages        = {902 -- 909},
  publisher    = {Cell Press},
  title        = {{Locally triggered release of the chemokine CCL21 promotes dendritic cell transmigration across lymphatic endothelia}},
  doi          = {10.1016/j.celrep.2017.04.027},
  volume       = {19},
  year         = {2017},
}

@article{1154,
  abstract     = {Cellular locomotion is a central hallmark of eukaryotic life. It is governed by cell-extrinsic molecular factors, which can either emerge in the soluble phase or as immobilized, often adhesive ligands. To encode for direction, every cue must be present as a spatial or temporal gradient. Here, we developed a microfluidic chamber that allows measurement of cell migration in combined response to surface immobilized and soluble molecular gradients. As a proof of principle we study the response of dendritic cells to their major guidance cues, chemokines. The majority of data on chemokine gradient sensing is based on in vitro studies employing soluble gradients. Despite evidence suggesting that in vivo chemokines are often immobilized to sugar residues, limited information is available how cells respond to immobilized chemokines. We tracked migration of dendritic cells towards immobilized gradients of the chemokine CCL21 and varying superimposed soluble gradients of CCL19. Differential migratory patterns illustrate the potential of our setup to quantitatively study the competitive response to both types of gradients. Beyond chemokines our approach is broadly applicable to alternative systems of chemo- and haptotaxis such as cells migrating along gradients of adhesion receptor ligands vs. any soluble cue. 
},
  author       = {Schwarz, Jan and Bierbaum, Veronika and Merrin, Jack and Frank, Tino and Hauschild, Robert and Bollenbach, Mark Tobias and Tay, Savaş and Sixt, Michael K and Mehling, Matthias},
  journal      = {Scientific Reports},
  publisher    = {Nature Publishing Group},
  title        = {{A microfluidic device for measuring cell migration towards substrate bound and soluble chemokine gradients}},
  doi          = {10.1038/srep36440},
  volume       = {6},
  year         = {2016},
}