Polarization of endosomal SNX27 in migrating and tumor-engaged natural killer cells.
Polarization is a critical mechanism for the proper functioning of many cell types. For lymphocytes, it is essential in a variety of processes, including migration from the blood to other tissue sites and vice versa. In NK cells and CTLs, the cytotoxic granule delivery mechanism requires polarization for granule movement to the immunological synapse (IS), in killing tumor and virus-infected cells. Recently, it has become apparent that endosomes are also involved in the cytotoxic mechanism. Using an in vitro conjugation approach, we show that in NK-92 cells, endosomal Sorting Nexin 27 (SNX27) polarizes to the IS during tumor cell engagement in a distinct compartment adjacent to the cytotoxic granules. We also show that SNX27 polarizes to the apical membrane, opposite the uropod, during NK cell migration. These previously unreported results indicate that SNX27 is a participant in NK cell polarization, as a mediator or target of the mechanism.
MacNeil
Adam J
AJ
Department of Biology, Dalhousie University, 1355 Oxford Street, Halifax, NS, Canada B3H 4J1.
Pohajdak
Bill
B
D002460:Cell Line; D002465:Cell Movement; D016764:Cell Polarity; D011992:Endosomes / Q000737:chemistry*; D006801:Humans; D020014:K562 Cells; D007694:Killer Cells, Natural / Q000276:immunology* / Q000648:ultrastructure; D008562:Membrane Glycoproteins / Q000032:analysis; D009369:Neoplasms / Q000276:immunology*; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins / Q000032:analysis; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins / Q000032:analysis*
D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; C522885:SNX27 protein, human; D058305:Sorting Nexins; D033921:Vesicular Transport Proteins; D054353:Perforin