Cytoskeletal interactions regulate inducible L-selectin clustering

Polly E. Mattila, Chad E. Green, Ulrich Schaff, Scott I. Simon, Bruce Walcheck

Research output: Contribution to journalArticle

18 Scopus citations

Abstract

L-selectin (CD62L) amplifies neutrophil capture within the microvasculature at sites of inflammation. Activation by G protein-coupled stimuli or through ligation of L-selectin promotes clustering of L-selectin and serves to increase its adhesiveness, signaling, and colocalization with β2- integrins. Currently, little is known about the molecular process regulating the lateral mobility of L-selectin. On neutrophil stimulation, a progressive change takes place in the organization of its plasma membrane, resulting in membrane domains that are characteristically enriched in glycosyl phosphatidylinositol (GPI)-anchored proteins and exclude the transmembrane protein CD45. Clustering of L-selectin, facilitated by E-selectin engagement or antibody cross-linking, resulted in its colocalization with GPI-anchored CD55, but not with CD45 or CD11c. Disrupting microfilaments in neutrophils or removing a conserved cationic motif in the cytoplasmic domain of L-selectin increased its mobility and membrane domain localization in the plasma membrane. In addition, the conserved element was critical for L-selectin-dependent tethering under shear flow. Our data indicate that L-selectin's lateral mobility is regulated by interactions with the actin cytoskeleton that in turn fortifies leukocyte tethering. We hypothesize that both membrane mobility and stabilization augment L-selectin's effector functions and are regulated by dynamic associations with membrane domains and the actin cytoskeleton.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Cell Physiology
Volume289
Issue number2 58-2
DOIs
StatePublished - Aug 2005

Keywords

  • Adhesion
  • Inflammation
  • Leukocyte
  • Membrane domains

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

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