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

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...

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Veröffentlicht in:Cell 2018-01, Vol.172 (1-2), p.305-317.e10
Hauptverfasser: 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
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Sprache:eng
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Zusammenfassung: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. [Display omitted] •CD44 functions as a picket, affixing the cortical actin cytoskeleton to the membrane•The extracellular domain of CD44 binds hyaluronan, which forms a pericellular coat•The picket fence and pericellular coat limit the mobility of phagocytic receptors•Remodeling of the actin fence enables receptors to cluster and initiate phagocytosis 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.
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2017.12.023