Survival of mycobacteria in macrophages is mediated by coronin 1-dependent activation of calcineurin

Jayachandran, R. and Sundaramurthy, V. and Combaluzier, B. and Mueller, P. and Korf, H. and Huygen, K. and Miyazaki, T. and Albrecht, I. and Massner, J. and Pieters, J.. (2007) Survival of mycobacteria in macrophages is mediated by coronin 1-dependent activation of calcineurin. Cell, 130 (1). pp. 37-50.

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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 Ca(2+)-dependent phosphatase calcineurin, thereby blocking lysosomal delivery of mycobacteria. In the absence of coronin 1, calcineurin activity did not occur, resulting in lysosomal delivery and killing of mycobacteria. Furthermore, blocking calcineurin activation with cyclosporin A or FK506 led to lysosomal delivery and intracellular mycobacterial killing. These results demonstrate a role for coronin 1 in activating Ca(2+) dependent signaling processes in macrophages and reveal a function for calcineurin in the regulation of phagosome-lysosome fusion upon mycobacterial infection.
Faculties and Departments:05 Faculty of Science > Departement Biozentrum > Infection Biology > Biochemistry (Pieters)
UniBasel Contributors:Pieters, Jean
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Cell Press
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:26 Sep 2017 10:34
Deposited On:22 Mar 2012 13:22

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