Protein‐Tyrosine Kinase, Syk Accelerates Phagosome Maturation by Depolymerizing F‐Actin in Complement‐Mediated Phagocytosis

Abstract

Syk is a non‐receptor protein‐tyrosine kinase and primarily expressed in hematopoietic cells. We previously reported that Syk plays an essential role in complement‐mediated phagocytosis, especially in engulfment process. In the current study, we aimed at clarifying the role of Syk in phagosome maturation process in complement‐mediated phagocytosis. To reveal the role of Syk in the phagocytosis, we established various Syk‐knockout (Syk‐KO) cell lines by using CRISPR/Cas9 system in HL60 cells. Using these parental and mutant HL60 cells, we performed complement‐mediated phagocytosis assay after macrophage‐like differentiation. As a result, we found that Syk‐KO macrophages permitted escape of C. albicans from the phagosomes because of the insufficient phagosome acidification. Additionally, we found that fusion of phagosomes with lysosomes did not occur in Syk‐KO cells and phagosomes of Syk‐KO cells still remained surrounded by thick F‐actin structure after engulfment process. These results demonstrate that Syk accelerates phagosome acidification by facilitating the collapse of F‐actin surrounding phagosomes and resultant fusion of lysosomes to the phagosomes in complement‐mediated phagocytosis. In conclusion, our results indicate that actin‐remodeling is essential not only for phagosome formation but also for phagosome maturation process in complement‐mediated phagocytosis.Support or Funding InformationThis work was supported by JSPS KAKENHI Grant Number JP 18K07432.