TY - JOUR
T1 - Actin cytoskeleton reorganization by syk regulates fcγ receptor responsiveness by increasing its lateral mobility and clustering
AU - Jaumouillé, Valentin
AU - Farkash, Yoav
AU - Jaqaman, Khuloud
AU - Das, Raibatak
AU - Lowell, Clifford A.
AU - Grinstein, Sergio
N1 - Funding Information:
This work was supported by grants MOP7075 and MOP102474 from the Canadian Institutes of Health Research (CIHR) to S.G and by grants RO1 AI 068150 and RO1 AI 065495 from the National Institutes of Health to C.A.L. V.J. was supported by the Heart and Stroke Foundation of Canada fellowship, the Fondation Bettencourt Schueller, and Cystic Fibrosis Canada. K.J. is a Deborah and W.A. “Tex” Moncrief, Jr. Scholar in Medical Research.
PY - 2014/6/9
Y1 - 2014/6/9
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84901997345&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84901997345&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2014.04.031
DO - 10.1016/j.devcel.2014.04.031
M3 - Article
C2 - 24914558
AN - SCOPUS:84901997345
SN - 1534-5807
VL - 29
SP - 534
EP - 546
JO - Developmental cell
JF - Developmental cell
IS - 5
ER -