LFA1 Activation: Insights from a Single-Molecule Approach

Cells. 2022 May 26;11(11):1751. doi: 10.3390/cells11111751.


Integrin LFA1 is a cell adhesion receptor expressed exclusively in leukocytes, and plays crucial roles in lymphocyte trafficking, antigen recognition, and effector functions. Since the discovery that the adhesiveness of LFA1 can be dynamically changed upon stimulation, one challenge has been understanding how integrins are regulated by inside-out signaling coupled with macromolecular conformational changes, as well as ligand bindings that transduce signals from the extracellular domain to the cytoplasm in outside-in signaling. The small GTPase Rap1 and integrin adaptor proteins talin1 and kindlin-3 have been recognized as critical molecules for integrin activation. However, their cooperative regulation of integrin adhesiveness in lymphocytes requires further research. Recent advances in single-molecule imaging techniques have revealed dynamic molecular processes in real-time and provided insight into integrin activation in cellular environments. This review summarizes integrin regulation and discusses new findings regarding the bidirectionality of LFA1 activation and signaling processes in lymphocytes.

Keywords: LFA1; Rap1; kindlin-3; talin.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing* / metabolism
  • Cell Adhesion
  • Integrins* / metabolism
  • Leukocytes / metabolism
  • Signal Transduction / physiology


  • Adaptor Proteins, Signal Transducing
  • Integrins

Grants and funding

This study was funded by JSPS KAKENHI Grant Numbers 25291047 (to T.K.), 20K07331, 17K18253, 15K21524 (to N.K.), 20K07554, and 16K08849 (to Y.U.); Grants-in-Aid for Scientific Research on Innovative Areas 22111003 (to T.K.) and 25113720 (to Y.U.); and the research grant “Private University Research Branding Project on intractable immune and allergic diseases” from Kansai Medical University (to T.K.).