Calcineurin activation spares invading Mycobacterium from death

addict submitted, created time 1 year 5 months (www.cell.com)

Pathogenic mycobacteria survive within macrophages by avoiding lysosomal delivery, instead residing in mycobacterial phagosomes. Upon infection, the leukocyte-specific protein coronin 1 is actively recruited to mycobacterial phagosomes, where it blocks lysosomal delivery by an unknown mechanism. Analysis of macrophages from coronin 1-deficient mice showed that coronin 1 is dispensable for F-actin-dependent processes such as phagocytosis, motility, and membrane ruffling. However, upon mycobacterial infection, coronin 1 was required for activation of the Ca2+-dependent phosphatase calcineurin, thereby blocking lysosomal delivery of mycobacteria. These results demonstrate a role for coronin 1 in activating Ca2+ dependent signaling processes in macrophages and reveal a function for calcineurin in the regulation of phagosome-lysosome fusion upon mycobacterial infection.

Keywords: Mycobacteria Calcineurin