A vesicle surface tyrosine kinase regulates phagosome maturation.
Phagocytosis is crucial for host defense against microbial pathogens and for obtaining nutrients in Dictyostelium discoideum. Phagocytosed particles are delivered via a complex route from phagosomes to lysosomes for degradation, but the molecular mechanisms involved in the phagosome maturation process are not well understood. Here, we identify a novel vesicle-associated receptor tyrosine kinase-like protein, VSK3, in D. discoideum. We demonstrate how VSK3 is involved in phagosome maturation. VSK3 resides on the membrane of late endosomes/lysosomes with its C-terminal kinase domain facing the cytoplasm. Inactivation of VSK3 by gene disruption reduces the rate of phagocytosis in cells, which is rescued by re-expression of VSK3. We found that the in vivo function of VSK3 depends on the presence of the kinase domain and vesicle localization. Furthermore, VSK3 is not essential for engulfment, but instead, is required for the fusion of phagosomes with late endosomes/lysosomes. Our findings suggest that localized tyrosine kinase signaling on the surface of endosome/lysosomes represents a control mechanism for phagosome maturation.
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health (NIH), Rockville, MD 20852, USA.
Jun
J
Fang
Joseph A
JA
Brzostowski
Stephen
S
Ou
Nilgun
N
Isik
Vinod
V
Nair
Tian
T
Jin
D000818:Animals; D004023:Dictyostelium / Q000166:cytology* / Q000201:enzymology* / Q000235:genetics; D008247:Lysosomes / Q000378:metabolism / Q000648:ultrastructure; D008561:Membrane Fusion / Q000502:physiology; D010587:Phagocytosis / Q000502:physiology; D010588:Phagosomes / Q000378:metabolism* / Q000648:ultrastructure; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015800:Protozoan Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D015800:Protozoan Proteins; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases