RAPL, a Rap1-binding molecule that mediates Rap1-induced adhesion through spatial regulation of LFA-1

Nat Immunol. 2003 Aug;4(8):741-8. doi: 10.1038/ni950. Epub 2003 Jul 6.

Abstract

The small GTPase Rap1 is a potent activator of leukocyte integrin. However, the regulatory mechanism involved is unknown. Here, we identify the Rap1 effector, RAPL, as an essential regulator in this activation. RAPL was enriched in mouse lymphoid tissues and associated with Rap1 after stimulation by the T cell receptor and with chemokine CXCL12. Human RAPL stimulated lymphocyte polarization and the patch-like redistribution of lymphocyte-function-associated antigen 1 (LFA-1) to the leading edge, resulting in enhanced adhesion to intercellular adhesion molecule 1 (ICAM-1). Triggered by activated Rap1, RAPL associated with LFA-1 and rapidly relocated to the leading edge and accumulated at immunological synapses. Thus, RAPL regulates lymphocyte adhesion through the spatial distribution of LFA-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • Apoptosis Regulatory Proteins
  • Cell Adhesion / immunology
  • Cell Adhesion / physiology*
  • Humans
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Mice
  • Molecular Sequence Data
  • Monomeric GTP-Binding Proteins
  • Receptors, Antigen, T-Cell / metabolism
  • T-Lymphocytes / physiology*
  • rap1 GTP-Binding Proteins / genetics
  • rap1 GTP-Binding Proteins / metabolism*

Substances

  • Adaptor Proteins, Signal Transducing
  • Apoptosis Regulatory Proteins
  • Lymphocyte Function-Associated Antigen-1
  • RAPL protein, mouse
  • RASSF5 protein, human
  • Receptors, Antigen, T-Cell
  • Monomeric GTP-Binding Proteins
  • rap1 GTP-Binding Proteins

Associated data

  • GENBANK/AY261332
  • GENBANK/AY261333