Transmembrane Pickets Connect Cyto- and Pericellular Skeletons Forming Barriers to Receptor Engagement

Spencer A. Freeman, Anthony Vega, Magdalena Riedl, Richard F. Collins, Phillip P. Ostrowski, Elliot C. Woods, Carolyn R. Bertozzi, Markku I. Tammi, Diane S. Lidke, Pauline Johnson, Satyajit Mayor, Khuloud Jaqaman, Sergio Grinstein

Research output: Contribution to journalArticle

49 Scopus citations

Abstract

Phagocytic receptors must diffuse laterally to become activated upon clustering by multivalent targets. Receptor diffusion, however, can be obstructed by transmembrane proteins (“pickets”) that are immobilized by interacting with the cortical cytoskeleton. The molecular identity of these pickets and their role in phagocytosis have not been defined. We used single-molecule tracking to study the interaction between Fcγ receptors and CD44, an abundant transmembrane protein capable of indirect association with F-actin, hence likely to serve as a picket. CD44 tethers reversibly to formin-induced actin filaments, curtailing receptor diffusion. Such linear filaments predominate in the trailing end of polarized macrophages, where receptor mobility was minimal. Conversely, receptors were most mobile at the leading edge, where Arp2/3-driven actin branching predominates. CD44 binds hyaluronan, anchoring a pericellular coat that also limits receptor displacement and obstructs access to phagocytic targets. Force must be applied to traverse the pericellular barrier, enabling receptors to engage their targets. The actin cytoskeleton is affixed to the plasma membrane by a cell-surface protein bound to a pericellular coat, forming a barrier that limits receptor mobility.

Original languageEnglish (US)
Pages (from-to)305-312.e10
JournalCell
Volume172
Issue number1-2
DOIs
StatePublished - Jan 11 2018

Keywords

  • Arp2/3
  • CD44
  • diffusion barrier
  • ezrin
  • Fc receptor
  • formin
  • glycocalyx
  • hyaluronan
  • phagocytosis
  • single particle tracking

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Freeman, S. A., Vega, A., Riedl, M., Collins, R. F., Ostrowski, P. P., Woods, E. C., Bertozzi, C. R., Tammi, M. I., Lidke, D. S., Johnson, P., Mayor, S., Jaqaman, K., & Grinstein, S. (2018). Transmembrane Pickets Connect Cyto- and Pericellular Skeletons Forming Barriers to Receptor Engagement. Cell, 172(1-2), 305-312.e10. https://doi.org/10.1016/j.cell.2017.12.023