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

Michael S Zhang1, Phuong M Tran1, Alexander J Wolff1

  • 1Department of Microbiology and Immunology, University of Iowa, Iowa City, IA 52242, USA.

Science Signaling
|May 3, 2018
PubMed

Insights

Glycerol monolaurate (GML) suppresses T cell function by disrupting actin cytoskeleton rearrangements. GML causes T cells to form filopodia instead of actin rings, impairing cell adhesion and migration.

Area of Science:

  • Immunology
  • Cell Biology
  • Biochemistry

Background:

  • Glycerol monolaurate (GML) is a monoglyceride known for its antimicrobial properties.
  • GML suppresses T cell receptor (TCR)-induced signaling and effector functions.
  • Actin cytoskeleton rearrangement is crucial for T cell interactions, migration, and effector functions.

Purpose of the Study:

  • To investigate the effect of GML on actin cytoskeleton rearrangement following TCR activation in human T cells.
  • To elucidate the molecular mechanisms by which GML interferes with TCR-induced actin dynamics.

Main Methods:

  • Treated human T cells with GML and activated TCR signaling.
  • Utilized microscopy techniques, including total internal reflection fluorescence microscopy (TIRFM), to visualize actin and protein microclusters.
  • Analyzed the localization and colocalization of key proteins involved in actin polymerization and TCR signaling.

Main Results:

  • GML-treated T cells exhibited reduced adherence and failed to form actin ring structures upon TCR activation.
  • Instead of normal actin structures, GML-treated cells developed numerous filopodia.
  • TIRFM revealed mislocalization of Arp2 microclusters in GML-treated cells, while SLP-76 and WASp microclusters showed altered colocalization patterns.

Conclusions:

  • Glycerol monolaurate (GML) significantly alters actin cytoskeletal rearrangements in T cells.
  • GML's T cell-suppressive effects are mediated, in part, by disrupting Arp2 microcluster organization and subsequent actin dynamics.
  • These findings identify novel mechanisms for GML's immunomodulatory functions.

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