RESUMO
There is an urgent need to develop new drugs against parasitic nematodes, which are a significant burden on human health and agriculture. Information about the function of essential nematode-specific genes provides insight to key nematode-specific processes that could be targeted with drugs. We have characterized the function of a novel, nematode-specific Caenorhabditis elegans protein, VHA-19, and show that VHA-19 is essential in the germline and, specifically, the oocytes, for the completion of embryogenesis. VHA-19 is also involved in trafficking the oocyte receptor RME-2 to the oocyte plasma membrane and is essential for osmoregulation in the embryo, probably because VHA-19 is required for proper eggshell formation via exocytosis of cortical granules or other essential components of the eggshell. VHA-19 may also have a role in cytokinesis, either directly or as an indirect effect of its role in osmoregulation. Critically, VHA-19 is expressed in the excretory cell in both larvae and adults, suggesting that it may have a role in osmoregulation in C. elegans more generally, probably in trafficking or secretion pathways. This is the first time a role for VHA-19 has been described.
Assuntos
Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/metabolismo , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/fisiologia , Oócitos/metabolismo , Equilíbrio Hidroeletrolítico/fisiologia , Animais , Transporte Biológico/fisiologia , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Membrana Celular/genética , Membrana Celular/metabolismo , Humanos , Oócitos/citologiaRESUMO
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.
