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Cell. 2018 Jan 11;172(1-2):305-317.e10. doi: 10.1016/j.cell.2017.12.023.

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

Author information

1
Program in Cell Biology, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada.
2
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
3
Departments of Chemistry and Molecular Biology and Howard Hughes Medical Institute, University of California, Berkeley, Berkeley, CA 94720, USA.
4
Institute of Biomedicine, University of Eastern Finland, Kuopio 70210, Finland.
5
Department of Pathology, Cancer Research Facility, School of Medicine, University of New Mexico, Albuquerque, NM 87131, USA.
6
Department of Microbiology and Immunology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
7
Cellular Organization and Signaling, National Centre for Biological Science, Tata Institute for Fundamental Research, Bangalore 560 065, India.
8
Program in Cell Biology, Peter Gilgan Centre for Research and Learning, Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON M5C 1N8, Canada. Electronic address: sergio.grinstein@sickkids.ca.

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.

KEYWORDS:

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

PMID:
29328918
PMCID:
PMC5929997
DOI:
10.1016/j.cell.2017.12.023
[Indexed for MEDLINE]
Free PMC Article

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