Minireview: The role of the vacuolar ATPase in nematodes

• Published in: Experimental parasitology Vol. 132; no. 1; pp. 47 - 55
• Main Authors: Knight, Alison J., Behm, Carolyn A.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.09.2012
• Subjects: adenosine triphosphate; Animals; Caenorhabditis elegans; Drug target; drugs; H-transporting ATP synthase; human health; Humans; hydrolysis; Nematoda; Nematoda - drug effects; Nematoda - enzymology; Nematoda - physiology; Nematode; neurophysiology; Neurotransmitter Agents - metabolism; nutrition; Osmoregulation; parasites; parasitology; protons; pumps; Reproduction; Vacuolar ATPase; Vacuolar Proton-Translocating ATPases - chemistry; Vacuolar Proton-Translocating ATPases - drug effects; Vacuolar Proton-Translocating ATPases - metabolism; Water-Electrolyte Balance; Drug target; Osmoregulation; Caenorhabditis elegans; Nematode; Reproduction; Vacuolar ATPase
• ISSN: 0014-4894; 1090-2449
• DOI: 10.1016/j.exppara.2011.09.004

[Display omitted] ► The V-ATPase is an enzyme complex with diverse cellular roles. ► Nematode V-ATPases are involved in many essential processes. ► Three key processes are osmoregulation, cuticle secretion and nutrient absorption. ► The nematode V-ATPase could provide a nematode drug target. ► Libraries of V-ATPase inhibitors exist; they should be screened in nematodes. The vacuolar ATPase enzyme complex (V-ATPase) pumps protons across membranes, energised by hydrolysis of ATP. It is involved in many physiological processes and has been implicated in many different diseases. While the broader functions of V-ATPases have been reviewed extensively, the role of this complex in nematodes specifically has not. Here, the essential role of the V-ATPase in nematode nutrition, osmoregulation, synthesis of the cuticle, neurobiology and reproduction is discussed. Based on the requirement of V-ATPase activity, or components of the V-ATPase, for these processes, the potential of the V-ATPase as a drug target for nematode parasites, which cause a significant burden to human health and agriculture, is also discussed. The V-ATPase has all the characteristics of a suitable drug target against nematodes, however the challenge will be to develop a high-throughput assay with which to test potential inhibitors.