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

Michael S Zhang; Phuong M Tran; Alexander J Wolff; Mikaela M Tremblay; Micaela G Fosdick; Jon C D Houtman

doi:10.1126/scisignal.aam9095

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

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

Michael S Zhang, Phuong M Tran, Alexander J Wolff, Mikaela M Tremblay, Micaela G Fosdick and Jon C D Houtman

Science signaling, Vol.11(528), p.eaam9095

05/01/2018

DOI: 10.1126/scisignal.aam9095

PMCID: PMC6048963

PMID: 29717064

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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.

Actin Cytoskeleton - metabolism

Receptors, Antigen, T-Cell - metabolism

Humans

Cells, Cultured

Monoglycerides - pharmacology

Cell Adhesion - drug effects

Phosphoproteins - metabolism

Surface-Active Agents - pharmacology

Pseudopodia - drug effects

Microscopy, Fluorescence - methods

Pseudopodia - metabolism

Signal Transduction - drug effects

T-Lymphocytes - metabolism

Actin Cytoskeleton - drug effects

Lymphocyte Activation - drug effects

T-Lymphocytes - drug effects

Wiskott-Aldrich Syndrome Protein - metabolism

Laurates - pharmacology

Membrane Proteins - metabolism

Adaptor Proteins, Signal Transducing - metabolism

Details

Title: Subtitle: Glycerol monolaurate induces filopodia formation by disrupting the association between LAT and SLP-76 microclusters
Creators: Michael S Zhang - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA
Phuong M Tran - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA
Alexander J Wolff - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA
Mikaela M Tremblay - Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA
Micaela G Fosdick - Biomedical Sciences Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Jon C D Houtman - Biomedical Sciences Program, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA
Resource Type: Journal article
Publication Details: Science signaling, Vol.11(528), p.eaam9095
DOI: 10.1126/scisignal.aam9095
PMID: 29717064
PMCID: PMC6048963
ISSN: 1945-0877
eISSN: 1937-9145
Grant note: R56 AI126493 / NIAID NIH HHS T32 AI007343 / NIAID NIH HHS T32 GM007337 / NIGMS NIH HHS P30 CA086862 / NCI NIH HHS R01 CA136729 / NCI NIH HHS
Language: English
Date published: 05/01/2018
Academic Unit: Microbiology and Immunology; Internal Medicine
Record Identifier: 9984094567902771

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