The Actin-Disassembly Protein Glia Maturation Factor γ Enhances Actin Remodeling and B Cell Antigen Receptor Signaling at the Immune Synapse

Signaling by the B cell antigen receptor (BCR) initiates actin remodeling. The assembly of branched actin networks that are nucleated by the Arp2/3 complex exert outward force on the plasma membrane, allowing B cells to form membrane protrusions that can scan the surface of antigen-presenting cells (APCs). The resulting Arp2/3 complex-dependent actin retrograde flow promotes the centripetal movement and progressive coalescence of BCR microclusters, which amplifies BCR signaling. Glia maturation factor gamma (GMF gamma) is an actin disassembly-protein that releases Arp2/3 complex-nucleated actin filaments from actin networks. By doing so, GMF gamma could either oppose the actions of the Arp2/3 complex or support Arp2/3 complex-nucleated actin polymerization by contributing to the recycling of actin monomers and Arp2/3 complexes. We now show that reducing the levels of GMF gamma in human B cell lines via transfection with a specific siRNA impairs the ability of B cells to spread on antigen-coated surfaces, decreases the velocity of actin retrograde flow, diminishes the coalescence of BCR microclusters into a central cluster at the B cell-APC contact site, and decreases APC-induced BCR signaling. These effects of depleting GMF gamma are similar to what occurs when the Arp2/3 complex is inhibited. This suggests that GMF gamma cooperates with the Arp2/3 complex to support BCR-induced actin remodeling and amplify BCR signaling at the immune synapse.

Automated summary

Signaling through the B cell antigen receptor (BCR) triggers actin remodeling, with the Arp2/3 complex nucleating branched actin networks that exert outward force on the plasma membrane. Glia maturation factor gamma (GMF gamma) functions as an actin disassembly protein, releasing actin filaments to either oppose or support Arp2/3 complex-nucleated actin polymerization. Depletion of GMF gamma in human B cell lines impairs cell spreading, reduces actin retrograde flow velocity, diminishes BCR microclusters coalescence, and decreases BCR signaling, similar to Arp2/3 complex inhibition.