Canonical and noncanonical g-protein signaling helps coordinate actin dynamics to promote macrophage phagocytosis of zymosan.

ABSTRACT: Both chemotaxis and phagocytosis depend upon actin-driven cell protrusions and cell membrane remodeling. While chemoattractant receptors rely upon canonical G-protein signaling to activate downstream effectors, whether such signaling pathways affect phagocytosis is contentious. Here, we report that G?i nucleotide exchange and signaling helps macrophages coordinate the recognition, capture, and engulfment of zymosan bioparticles. We show that zymosan exposure recruits F-actin, G?i proteins, and Elmo1 to phagocytic cups and early phagosomes. Zymosan triggered an increase in intracellular Ca(2+) that was partially sensitive to G?i nucleotide exchange inhibition and expression of GTP-bound G?i recruited Elmo1 to the plasma membrane. Reducing GDP-G?i nucleotide exchange, decreasing G?i expression, pharmacologically interrupting G?? signaling, or reducing Elmo1 expression all impaired phagocytosis, while favoring the duration that G?i remained GTP bound promoted it. Our studies demonstrate that targeting heterotrimeric G-protein signaling offers opportunities to enhance or retard macrophage engulfment of phagocytic targets such as zymosan.

SUBMITTER: Huang NN 

PROVIDER: S-EPMC4248717 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature