Activation of Raf/MEK/ERK/cPLA2 signaling pathway is essential for chlamydial acquisition of host glycerophospholipids.
Chlamydiae, a diverse group of obligate intracellular pathogens replicating within cytoplasmic vacuoles of eukaryotic cells, are able to acquire lipids from host cells. Here we report that activation of the host Raf-MEK-ERK-cPLA2 signaling cascade is required for the chlamydial uptake of host glycerophospholipids. Both the MAP kinase pathway (Ras/Raf/MEK/ERK) and Ca(2+)-dependent cytosolic phospholipase A2 (cPLA2) were activated in chlamydia-infected cells. The inhibition of cPLA2 activity resulted in the blockade of the chlamydial uptake of host glycerophospholipids and impairment in chlamydial growth. Blocking either c-Raf-1 or MEK1/2 activity prevented the chlamydial activation of ERK1/2, leading to the suppression of both chlamydial activation of the host cPLA2 and uptake of glycerophospholipids from the host cells. The chlamydia-induced phosphorylation of cPLA2 was also blocked by a dominant negative ERK2. Furthermore, activation of both ERK1/2 and cPLA2 was dependent on chlamydial growth and restricted within chlamydia-infected cells, suggesting an active manipulation of the host ERK-cPLA2 signaling pathway by chlamydiae.
Su
Heng
H
Department of Microbiology and Immunology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA.
McClarty
Grant
G
Dong
Feng
F
Hatch
Grant M
GM
Pan
Zhixing K
ZK
Zhong
Guangming
G
D002460:Cell Line; D002689:Chlamydia / Q000254:growth & development / Q000378:metabolism; D002690:Chlamydia Infections / Q000378:metabolism* / Q000382:microbiology; D020404:Glycerophospholipids / Q000378:metabolism*; D006801:Humans; D048728:MAP Kinase Kinase Kinase 1; D020930:MAP Kinase Kinase Kinases / Q000378:metabolism; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D019908:Proto-Oncogene Proteins c-raf / Q000378:metabolism; D015398:Signal Transduction
D020404:Glycerophospholipids; D019908:Proto-Oncogene Proteins c-raf; D020928:Mitogen-Activated Protein Kinases; D048728:MAP Kinase Kinase Kinase 1; D020930:MAP Kinase Kinase Kinases; C482576:MAP3K1 protein, human; D010741:Phospholipases A; D054467:Phospholipases A2