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Integrin LFA-1 regulates cell adhesion via transient clutch formation

Munenori Ishibashi1, Yukihiro Miyanaga1, Satomi Matsuoka1

  • 1Laboratory for Cell Signaling Dynamics, QBiC (Quantitative Biology Center), RIKEN, 6-2-3 Furuedai, Suita, Osaka 565-0874, Japan; Department of Biological Sciences, Graduate School of Science, Osaka University, 1-1 Machikaneyama, Toyonaka, Osaka 560-0043, Japan.

Biochemical and Biophysical Research Communications
|July 6, 2015
PubMed

Insights

Transient molecular clutch formation by integrin LFA-1 is sufficient for immune cell adhesion. Fast cycling of this clutch, not stable binding, drives dynamic cell migration.

Area of Science:

  • Cellular biology
  • Immunology
  • Biophysics

Background:

  • Integrin LFA-1 (leukocyte function-associated antigen 1) is crucial for immune cell adhesion and trafficking, binding to ICAM-1 (intercellular adhesion molecule 1).
  • Integrin-mediated clutch formation, linking extracellular ligands to the intracellular actin cytoskeleton, is vital for stable cell adhesion.
  • Understanding the dynamics of this molecular clutch is key to deciphering immune cell migration.

Purpose of the Study:

  • To investigate the ligand-binding kinetics and molecular clutch mobility of LFA-1 and ICAM-1 in living cells.
  • To differentiate clutch dynamics under physiological (chemokine-induced) and high-affinity (Mn2+-induced) adhesion conditions.

Main Methods:

  • Single-molecule tracking analysis of LFA-1 and ICAM-1 in living cells.
  • Observation of molecular clutch formation and dynamics during chemokine-induced and Mn2+-induced adhesion.

Main Results:

  • Transient LFA-1-mediated clutch formation, lasting seconds, is sufficient for promoting cell adhesion.
  • Stable clutch formation was observed for high-affinity LFA-1 induced by Mn2+, but this was not necessary for physiological adhesion.
  • The transient nature of clutch formation allows for dynamic cell adhesion and migration.

Conclusions:

  • Fast cycling of integrin-mediated molecular clutches, rather than stable formation, underlies dynamic immune cell adhesion.
  • This dynamic clutch mechanism enables efficient cell migration and trafficking in response to physiological cues.

Keywords:
Cell adhesionChemokineImmune cellIntegrinSingle-molecule

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