Journal
DEVELOPMENTAL CELL
Volume 29, Issue 5, Pages 534-546Publisher
CELL PRESS
DOI: 10.1016/j.devcel.2014.04.031
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Funding
- Canadian Institutes of Health Research (CIHR) [MOP7075, MOP102474]
- National Institutes of Health [RO1 AI 068150, RO1 AI 065495]
- Heart and Stroke Foundation of Canada fellowship
- Fondation Bettencourt Schueller
- Cystic Fibrosis Canada
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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 Fc gamma receptors (Fc gamma R). 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 Fc gamma R. 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 Fc gamma R at the tip of pseudopods, directing the progression of phagocytosis.
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