Research ArticleCytoskeleton

Glycerol monolaurate induces filopodia formation by disrupting the association between LAT and SLP-76 microclusters

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Sci. Signal.  01 May 2018:
Vol. 11, Issue 528, eaam9095
DOI: 10.1126/scisignal.aam9095

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Monoglyceride spurs flawed actin rearrangement

Immune cells are sensitive to neutral fats that are often a common ingredient in cosmetics and food preservatives. The monolyceride glycerol monolaurate (GML) inhibits both bacterial growth and T cell receptor (TCR)–induced signaling. Zhang et al. investigated the effect of GML on actin cytoskeletal rearrangements in human T cells by TIRF microscopy and found that GML provoked erroneous filapodial formation after TCR stimulation. Cells treated with GML formed signaling microclusters that lacked an essential adaptor for actin rearrangement and mislocalized Arp2, a critical component of the actin polymerization complex. These data suggest that GML also suppresses T cell responses by preventing appropriate actin cytoskeletal rearrangements.

Abstract

Glycerol monolaurate (GML) is a monoglyceride with potent antimicrobial properties that suppresses T cell receptor (TCR)–induced signaling and T cell effector function. Actin rearrangement is needed for the interaction of T cells with antigen-presenting cells and for migration to sites of infection. Because of the critical role actin rearrangement plays in T cell effector function, we analyzed the effect of GML on the rearrangement of the actin cytoskeleton after TCR activation. We found that GML-treated human T cells were less adherent than untreated T cells and did not form actin ring structures but instead developed numerous inappropriate actin-mediated filopodia. The formation of these filopodia was not due to disruption of TCR-proximal regulators of actin or microtubule polymerization. Instead, total internal reflection fluorescence microscopy demonstrated mislocalization of actin nucleation protein Arp2 microclusters, but not those containing the adaptor proteins SLP-76 and WASp, or the actin nucleation protein ARPC3, which are necessary for TCR-induced actin rearrangement. Additionally, SLP-76 microclusters colocalized with WASp and WAVE microclusters but not with LAT. Together, our data suggest that GML alters actin cytoskeletal rearrangements and identify diverse functions for GML as a T cell–suppressive agent.

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