Down-regulation of MARCKS-related Protein (MRP) in Macrophages Infected withLeishmania

Sally Corradin, Jacques Mauël, Adriana Ransijn, Christoph Stürzinger, Guy Vergères
1999 Journal of Biological Chemistry  
Leishmania, a protozoan parasite of macrophages, has been shown to interfere with host cell signal transduction pathways including protein kinase C (PKC)dependent signaling. Myristoylated alanine-rich C kinase substrate (MARCKS) and MARCKS-related protein (MRP, MacMARCKS) are PKC substrates in diverse cell types. MARCKS and MRP are thought to regulate the actin network and thereby participate in cellular responses involving cytoskeletal rearrangement. Because MRP is a major PKC substrate in
more » ... ophages, we examined its expression in response to infection by Leishmania. Activation of murine macrophages by cytokines increased MRP expression as determined by Western blot analysis. Infection with Leishmania promastigotes at the time of activation or up to 48 h postactivation strongly decreased MRP levels. Leishmania-dependent MRP depletion was confirmed by [ 3 H]myristate labeling and by immunofluorescence microscopy. All species or strains of Leishmania parasites tested, including lipophosphoglycan-deficient Leishmania major L119, decreased MRP levels. MRP depletion was not obtained with other phagocytic stimuli including zymosan, latex beads, or heat-killed Streptococcus mitis, a Gram-positive bacterium. Experiments with [ 3 H]myristate labeled proteins revealed the appearance of lower molecular weight fragments in Leishmania-infected cells suggesting that MRP depletion may be due to proteolytic degradation.
doi:10.1074/jbc.274.24.16782 pmid:10358020 fatcat:fgclyyshsbckpo4uof3kxf5qhu