Potential role of Acanthamoeba Rab7

Acanthamoeba castellanii is a free-living protozoan that causes several severe human parasitic diseases such as Acanthamoeba keratitis and granulomatous encephalitis. A. castellanii feeds on bacteria, yeasts, and other organic particles as food sources, but the mechanisms of digestion in acanthamoebal cells are unclear. Rab GTPases participate in endosomal delivery in eukaryotes after phagocytosis. This study aimed to determine the potential functions of A. castellanii Rab7 (AcRab7), which is involved in phagocytosis, and the relationship between AcRab7 and further cellular physiological phenomena. In this study, the inhibitor CID1067700 (CID) was used to specifically inhibit the binding of nucleotides to confirm the potential functions of AcRab7. Cellular proliferation and ATP assays were also used to detect underlying cellular physiological functions after blocking the phagocytosis pathway. We found that AcRab7 expression increased as the co-culture time with Escherichia coli increased. Immunofluorescence staining showed that AcRab7 colocalized with lysosomes in its GTP-activating form. In addition, AcRab7 inhibition resulted in a reduction in cell proliferation and ATP levels. Our results suggest that AcRab7 participates in endosomal delivery and dominates energy production and cell growth.

 

Comments:

This study seems to shed light on the role of AcRab7 in Acanthamoeba castellanii's cellular processes, particularly in phagocytosis, endosomal delivery, and its impact on cellular physiology. AcRab7, a member of the Rab GTPase family, appears to be involved in endosomal delivery post-phagocytosis, suggesting its significance in the digestion process within these cells.

The use of CID1067700 to inhibit nucleotide binding in AcRab7 seems to have yielded significant findings. The increase in AcRab7 expression during co-culture with Escherichia coli implies its active involvement in response to bacterial presence, possibly indicating a role in the recognition or handling of bacterial particles.

The colocalization of AcRab7 with lysosomes in its GTP-activating form further supports its involvement in endosomal processes, likely contributing to the digestion of engulfed material within these cells.

The observed reduction in cell proliferation and ATP levels upon AcRab7 inhibition suggests a link between the phagocytosis pathway, energy production, and cell growth in A. castellanii. This implies that AcRab7 not only participates in endosomal delivery but also significantly influences cellular physiology, impacting the overall growth and energy metabolism of these protozoans.

These findings provide valuable insights into the functions of AcRab7 and its multifaceted roles in cellular processes, offering potential implications for understanding Acanthamoeba-related diseases and possibly identifying targets for therapeutic intervention.

Related Products

Cat.No.	Product Name	Information
E0135	CID-1067700 (ML282)	CID-1067700 (ML282) is a pan-GTPase inhibitor with a ki of 12.89 nM for Rab7wt.

Related Targets

Ras