| First Author | Huang NN | Year | 2014 |
| Journal | Mol Cell Biol | Volume | 34 |
| Issue | 22 | Pages | 4186-99 |
| PubMed ID | 25225330 | Mgi Jnum | J:224329 |
| Mgi Id | MGI:5662029 | Doi | 10.1128/MCB.00325-14 |
| Citation | Huang NN, et al. (2014) Canonical and noncanonical g-protein signaling helps coordinate actin dynamics to promote macrophage phagocytosis of zymosan. Mol Cell Biol 34(22):4186-99 |
| abstractText | 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 Galphai nucleotide exchange and signaling helps macrophages coordinate the recognition, capture, and engulfment of zymosan bioparticles. We show that zymosan exposure recruits F-actin, Galphai proteins, and Elmo1 to phagocytic cups and early phagosomes. Zymosan triggered an increase in intracellular Ca(2+) that was partially sensitive to Galphai nucleotide exchange inhibition and expression of GTP-bound Galphai recruited Elmo1 to the plasma membrane. Reducing GDP-Galphai nucleotide exchange, decreasing Galphai expression, pharmacologically interrupting Gbetagamma signaling, or reducing Elmo1 expression all impaired phagocytosis, while favoring the duration that Galphai 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. |
