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

28 Citations (Scopus)

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

Fingerprint

Actin Cytoskeleton
Skeleton
Actins
Immobilized Proteins
Fc Receptors
Hyaluronic Acid
Cytoskeleton
Phagocytosis
Cluster Analysis
Membrane Proteins
Macrophages
Cell Membrane
Cell membranes
Proteins
Molecules

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)

Cite this

Freeman, S. A., Vega, A., Riedl, M., Collins, R. F., Ostrowski, P. P., Woods, E. C., ... 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

Transmembrane Pickets Connect Cyto- and Pericellular Skeletons Forming Barriers to Receptor Engagement. / Freeman, Spencer A.; Vega, Anthony; Riedl, Magdalena; Collins, Richard F.; Ostrowski, Phillip P.; Woods, Elliot C.; Bertozzi, Carolyn R.; Tammi, Markku I.; Lidke, Diane S.; Johnson, Pauline; Mayor, Satyajit; Jaqaman, Khuloud; Grinstein, Sergio.

In: Cell, Vol. 172, No. 1-2, 11.01.2018, p. 305-312.e10.

Research output: Contribution to journalArticle

Freeman, SA, Vega, A, Riedl, M, Collins, RF, Ostrowski, PP, Woods, EC, Bertozzi, CR, Tammi, MI, Lidke, DS, Johnson, P, Mayor, S, Jaqaman, K & Grinstein, S 2018, 'Transmembrane Pickets Connect Cyto- and Pericellular Skeletons Forming Barriers to Receptor Engagement', Cell, vol. 172, no. 1-2, pp. 305-312.e10. https://doi.org/10.1016/j.cell.2017.12.023
Freeman SA, Vega A, Riedl M, Collins RF, Ostrowski PP, Woods EC et al. Transmembrane Pickets Connect Cyto- and Pericellular Skeletons Forming Barriers to Receptor Engagement. Cell. 2018 Jan 11;172(1-2):305-312.e10. https://doi.org/10.1016/j.cell.2017.12.023
Freeman, Spencer A. ; Vega, Anthony ; Riedl, Magdalena ; Collins, Richard F. ; Ostrowski, Phillip P. ; Woods, Elliot C. ; Bertozzi, Carolyn R. ; Tammi, Markku I. ; Lidke, Diane S. ; Johnson, Pauline ; Mayor, Satyajit ; Jaqaman, Khuloud ; Grinstein, Sergio. / Transmembrane Pickets Connect Cyto- and Pericellular Skeletons Forming Barriers to Receptor Engagement. In: Cell. 2018 ; Vol. 172, No. 1-2. pp. 305-312.e10.
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