Down-regulation of MARCKS-related protein (MRP) in macrophages infected with Leishmania.
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 macrophages, 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 [3H]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 [3H]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.
Corradin
S
S
Institute of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland. Sally.CorradinBetz@ib.unil.ch
Mauël
J
J
Ransijn
A
A
Stürzinger
C
C
Vergères
G
G
D000818:Animals; D001854:Bone Marrow Cells / Q000469:parasitology*; D002148:Calmodulin-Binding Proteins; D002451:Cell Compartmentation; D015536:Down-Regulation; D007371:Interferon-gamma / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D007891:Leishmania / Q000472:pathogenicity*; D007893:Leishmania donovani / Q000472:pathogenicity; D018320:Leishmania major / Q000472:pathogenicity; D007894:Leishmania mexicana / Q000472:pathogenicity; D008262:Macrophage Activation; D008264:Macrophages / Q000187:drug effects / Q000469:parasitology*; D008565:Membrane Proteins / Q000096:biosynthesis* / Q000302:isolation & purification; D051379:Mice; D008808:Mice, Inbred CBA; D008840:Microfilament Proteins; D010587:Phagocytosis; D011493:Protein Kinase C / Q000378:metabolism; D013045:Species Specificity; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D002148:Calmodulin-Binding Proteins; D047908:Intracellular Signaling Peptides and Proteins; C512945:Marcksl1 protein, mouse; D008565:Membrane Proteins; D008840:Microfilament Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011493:Protein Kinase C