Sci. Signal., 16 March 2010
Decoupling a MAPK PathwayChlamydia trachomatis (Ctr) is an obligate, intracellular bacterial pathogen that causes a number of sexually transmitted diseases and the infectious eye disease, trachoma. Ctr cycles between an extracellular, infectious state known as the elementary body and an intracellular, metabolically active and replicating state known as the reticulate body. Ctr reticulate bodies accumulate within the inclusion, a membrane-bound vacuole. Gurumurthy et al. performed an RNA interference (RNAi)–based screen of infected epithelial cells and identified 59 factors that regulated Ctr infectivity. Knockdown of two of these, K-Ras and Raf-1, resulted in the increased growth of Ctr. Infection by Ctr led to the phosphorylation and inactivation of Raf-1 and its recruitment to the inclusion rather than to the plasma membrane where it normally triggers the MEK-ERK pathway, which is important for cell survival. Despite the inactivation of Raf-1, ERK activation was normal in infected cells, ensuring survival of the cells and growth of the pathogen. Thus, Ctr differentially modulates components of the Ras-ERK pathway to its own advantage.
Citation: R. K. Gurumurthy, A. P. Mäurer, N. Machuy, S. Hess, K. P. Pleissner, J. Schuchhardt, T. Rudel, T. F. Meyer, A Loss-of-Function Screen Reveals Ras- and Raf-Independent MEK-ERK Signaling During Chlamydia trachomatis Infection. Sci. Signal. 3, ra21 (2010).
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