Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.1.3 (
ATPase
)
65,361
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
We recently showed that the exocytosis regulator Synaptotagmin (Syt) V is recruited to the nascent phagosome and remains associated throughout the maturation process. In this study, we investigated the possibility that
Syt V
plays a role in regulating interactions between the phagosome and the endocytic organelles. Silencing of
Syt V
by RNA interference revealed that
Syt V
contributes to phagolysosome biogenesis by regulating the acquisition of cathepsin D and the vesicular proton-
ATPase
. In contrast, recruitment of cathepsin B, the early endosomal marker EEA1 and the lysosomal marker LAMP1 to phagosomes was normal in the absence of
Syt V
. As Leishmania donovani promastigotes inhibit phagosome maturation, we investigated their potential impact on the phagosomal association of
Syt V
. This inhibition of phagolysosome biogenesis is mediated by the virulence glycolipid lipophosphoglycan, a polymer of the repeating Galbeta1,4Manalpha1-PO(4) units attached to the promastigote surface via an unusual glycosylphosphatidylinositol anchor. Our results showed that insertion of lipophosphoglycan into ganglioside GM1-containing microdomains excluded or caused dissociation of
Syt V
from phagosome membranes. As a consequence, L. donovani promatigotes established infection in a phagosome from which the vesicular proton-
ATPase
was excluded and which failed to acidify. Collectively, these results reveal a novel function for
Syt V
in phagolysosome biogenesis and provide novel insight into the mechanism of vesicular proton-
ATPase
recruitment to maturing phagosomes. We also provide novel findings into the mechanism of Leishmania pathogenesis, whereby targeting of
Syt V
is part of the strategy used by L. donovani promastigotes to prevent phagosome acidification.
...
PMID:The Leishmania donovani lipophosphoglycan excludes the vesicular proton-ATPase from phagosomes by impairing the recruitment of synaptotagmin V. 1983 55
