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New HIV/AIDS study findings reported from Y. Ding and co-authors
April 28th, 2008
2008 APR 28 -- "The CXC chemokine CXCL12 and its cognate receptor CXCR4 play an important role in inflammation, human immunodeficiency virus (HIV) infection and cancer metastasis. The signal transduction and intracellular trafficking of CXCR4 are involved in these functions, but the underlying mechanisms remain incompletely understood," scientists writing in the journal Experimental Cell Research report. "In the present study, we demonstrated that the CXCR4 formed a complex with the cytolinker protein plectin in a ligand-dependent manner in HEK293 cells stably expressing CXCR4. The glutathione-S-transferase (GST)-CXCR4 C-terminal fusion proteins co-precipitated with the full-length and the N-terminal fragments of plectin isoform 1 but not with the N-terminal deletion mutants of plectin isoform 1, thereby suggesting an interaction between the N-terminus of plectin and the C-terminus of CXCR4. This interaction was confirmed by confocal microscopic reconstructions showing co-distribution of these two proteins in the internal vesicles after ligand-induced internalization of CXCR4 in HEK293 cells stably expressing CXCR4. Knockdown of plectin with RNA interference (RNAi) significantly inhibited ligand-dependent CXCR4 internalization and attenuated CXCR4-mediated intracellular calcium mobilization and activation of extracellular signal regulated kinase 1/2 (ERK1/2). CXCL12-induced chemotaxis of HEK293 cells stably expressing CXCR4 and of Jurkat T cells was inhibited by the plectin RNAi. Moreover, CXCR4 tropic HIV-1 infection in MAGI (HeLa-CD4-LTR-Ga1) cells was inhibited by the RNAi of plectin," wrote Y. Ding and colleagues. The researchers concluded: "Thus, plectin appears to interact with CXCR4 and plays an important role in CXCR4 signaling and trafficking and HIV-1 infection." Ding and colleagues published their study in Experimental Cell Research (Plectlin regulates the signaling and trafficking of the HIV-1 co-receptor CXCR4 and plays a role in HIV-1 infection. Experimental Cell Research, 2008;314(3):590-602). Additional information can be obtained by contacting G.H. Fan, Dept. of Vet. Affairs, Nashville, TN 37212, USA. The publisher of the journal Experimental Cell Research can be contacted at: Elsevier Inc., 525 B Street, Ste. 1900, San Diego, CA 92101-4495, USA. Keywords: United States, Nashville, HIV/AIDS, AIDS, Acquired Immune Deficiency Syndrome, Acquired Immunodeficiency Syndrome, Cancer, Dietary Supplement, Enzyme Research, Glutathione, HIV, Human Immunodeficiency Virus, Immunology, Inflammation, Micronutrient, Oncology, Proteomics. Fusion Proteins, Sexually Transmitted Disease, Transferase, Viral, Virology. This article was prepared by AIDS Weekly editors from staff and other reports. Copyright 2008, AIDS Weekly via NewsRx.com.
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