RhoB controls the Rab11-mediated recycling and surface reappearance of LFA-1 in migrating T lymphocytes

Sci Signal. 2017 Dec 12;10(509):eaai8629. doi: 10.1126/scisignal.aai8629.

Abstract

The regulation of cell adhesion and motility is complex and requires the intracellular trafficking of integrins to and from sites of cell adhesion, especially in fast-moving cells such as leukocytes. The Rab family of guanosine triphosphatases (GTPases) is essential for vesicle transport, and vesicles mediate intracellular integrin trafficking. We showed that RhoB regulates the vesicular transport of the integrin LFA-1 along the microtubule network in migrating T lymphocytes. Impairment in RhoB function resulted in the accumulation of both LFA-1 and the recycling endosomal marker Rab11 at the rear of migrating T lymphocytes and decreased the association between these molecules. T lymphocytes lacking functional RhoB exhibited impaired recycling and subsequently decreased surface amounts of LFA-1, leading to reduced T cell adhesion and migration mediated by the cell adhesion molecule ICAM-1 (intercellular adhesion molecule-1). We propose that vesicle-associated RhoB is a regulator of the Rab11-mediated recycling of LFA-1 to the cell surface, an event that is necessary for T lymphocyte motility.

MeSH terms

  • Cell Adhesion
  • Cell Movement*
  • Cells, Cultured
  • Humans
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • T-Lymphocytes / cytology
  • T-Lymphocytes / metabolism*
  • rab GTP-Binding Proteins / metabolism*
  • rhoB GTP-Binding Protein / metabolism*

Substances

  • Lymphocyte Function-Associated Antigen-1
  • rab11 protein
  • rab GTP-Binding Proteins
  • rhoB GTP-Binding Protein