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Dev Cell. 2014 Jun 9;29(5):534-546. doi: 10.1016/j.devcel.2014.04.031.

Actin cytoskeleton reorganization by Syk regulates Fcγ receptor responsiveness by increasing its lateral mobility and clustering.

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Program in Cell Biology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada.
Department of Biophysics, University of Texas Southwestern Medical Center, Dallas, TX 75390-8816, USA.
Department of Integrative Biology, University of Colorado Denver, Denver, CO 80204, USA.
Department of Laboratory Medicine, University of California, San Francisco, San Francisco, CA 94143-0100, USA.
Program in Cell Biology, Hospital for Sick Children, Toronto, ON M5G1X8, Canada; Keenan Research Centre of the Li Ka Shing Knowledge Institute, St. Michael's Hospital, 209 Victoria Street, Toronto, ON M5C 1N8, Canada. Electronic address:


Clustering of immunoreceptors upon association with multivalent ligands triggers important responses including phagocytosis, secretion of cytokines, and production of immunoglobulins. We applied single-molecule detection and tracking methods to study the factors that control the mobility and clustering of phagocytic Fcγ receptors (FcγR). While the receptors exist as monomers in resting macrophages, two distinct populations were discernible based on their mobility: some diffuse by apparent free motion, while others are confined within submicron boundaries that reduce the frequency of spontaneous collisions. Src-family and Syk kinases determine the structure of the actin cytoskeleton, which is fenestrated, accounting for the heterogeneous diffusion of the FcγR. Stimulation of these kinases during phagocytosis induces reorganization of the cytoskeleton both locally and distally in a manner that alters receptor mobility and clustering, generating a feedback loop that facilitates engagement of FcγR at the tip of pseudopods, directing the progression of phagocytosis.

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