Surfing on Membrane Waves: Microvilli, Curved Membranes, and Immune Signaling

Front Immunol. 2020 Sep 11:11:2187. doi: 10.3389/fimmu.2020.02187. eCollection 2020.

Abstract

Microvilli are finger-like membrane protrusions, supported by the actin cytoskeleton, and found on almost all cell types. A growing body of evidence suggests that the dynamic lymphocyte microvilli, with their highly curved membranes, play an important role in signal transduction leading to immune responses. Nevertheless, challenges in modulating local membrane curvature and monitoring the high dynamicity of microvilli hampered the investigation of the curvature-generation mechanism and its functional consequences in signaling. These technical barriers have been partially overcome by recent advancements in adapted super-resolution microscopy. Here, we review the up-to-date progress in understanding the mechanisms and functional consequences of microvillus formation in T cell signaling. We discuss how the deformation of local membranes could potentially affect the organization of signaling proteins and their biochemical activities. We propose that curved membranes, together with the underlying cytoskeleton, shape microvilli into a unique compartment that sense and process signals leading to lymphocyte activation.

Keywords: BAR protein; T-cell signaling; TCR; WASp; actin; membrane curvature; microvilli; super-resolution microscopy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Actin Cytoskeleton / drug effects
  • Actin Cytoskeleton / ultrastructure
  • Animals
  • Carrier Proteins / pharmacology
  • Cell Line
  • Cell Membrane / drug effects
  • Cell Membrane / immunology*
  • Cell Membrane / ultrastructure
  • Cell Shape
  • Cyclodextrins / pharmacology
  • Cytokines / physiology
  • Glycocalyx / drug effects
  • Glycocalyx / immunology
  • Humans
  • Lymphocyte Activation / drug effects
  • Lymphocyte Activation / physiology*
  • Membrane Lipids / immunology
  • Membrane Proteins / immunology
  • Mice
  • Microfilament Proteins / pharmacology
  • Microscopy, Electron, Scanning
  • Microvilli / drug effects
  • Microvilli / immunology*
  • Microvilli / ultrastructure
  • Receptors, Antigen, T-Cell / immunology
  • Signal Transduction / drug effects
  • Signal Transduction / immunology*
  • Stress, Mechanical
  • Surface Properties
  • Synaptosomes / drug effects
  • Synaptosomes / immunology
  • Synaptosomes / ultrastructure
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology
  • T-Lymphocytes / ultrastructure*

Substances

  • Carrier Proteins
  • Cyclodextrins
  • Cytokines
  • Membrane Lipids
  • Membrane Proteins
  • Microfilament Proteins
  • Receptors, Antigen, T-Cell
  • fascin