Major vault protein regulates class A scavenger receptor-mediated tumor necrosis factor-α synthesis and apoptosis in macrophages.

TitleMajor vault protein regulates class A scavenger receptor-mediated tumor necrosis factor-α synthesis and apoptosis in macrophages.
Publication TypeJournal Article
Year of Publication2013
AuthorsBen J, Zhang Y, Zhou R, Zhang H, Zhu X, Li X, Zhang H, Li N, Zhou X, Bai H, Yang Q, Li D, Xu Y, Chen Q
JournalThe Journal of biological chemistry
Volume288
Issue27
Pagination20076-84
Date Published2013 Jul 5
Abstract

Atherosclerosis is considered a disease of chronic inflammation largely initiated and perpetuated by macrophage-dependent synthesis and release of pro-inflammatory mediators. Class A scavenger receptor (SR-A) expressed on macrophages plays a key role in this process. However, how SR-A-mediated pro-inflammatory response is modulated in macrophages remains ill defined. Here through immunoprecipitation coupled with mass spectrometry, we reported major vault protein (MVP) as a novel binding partner for SR-A. The interaction between SR-A and MVP was confirmed by immunofluorescence staining and chemical cross-linking assay. Treatment of macrophages with fucoidan, a SR-A ligand, led to a marked increase in TNF-α production, which was attenuated by MVP depletion. Further analysis revealed that SR-A stimulated TNF-α synthesis in macrophages via the caveolin- instead of clathrin-mediated endocytic pathway linked to p38 and JNK, but not ERK, signaling pathways. Importantly, fucoidan invoked an enrichment of MVP in lipid raft, a caveolin-reliant membrane structure, and enhanced the interaction among SR-A, caveolin, and MVP. Finally, we demonstrated that MVP elimination ameliorated SR-A-mediated apoptosis in macrophages. As such, MVP may fine-tune SR-A activity in macrophages which contributes to the development of atherosclerosis.

DOI10.1136/eb-2013-101292
Alternate JournalJ. Biol. Chem.