Abstract
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.
Highlights
Parasitic nematodes are a significant burden on human health [1] and cause large losses to agriculture [2]
VIT-2::GFP reached the surface of vha-19(RNAi) oocytes but was not endocytosed. As this phenotype was only observed in 7% of VIT-2::GFP; control(RNAi) adults (n = 89), these results suggest that VHA-19 might be involved in either receptor-mediated endocytosis directly, or in the trafficking of RME-2, the receptor required for this process
We have characterized the physiological and developmental roles of the novel C. elegans protein VHA-19 and have shown that it is essential in the oocytes for successful embryogenesis
Summary
Parasitic nematodes are a significant burden on human health [1] and cause large losses to agriculture [2]. We identified VHA-19 in a screen for essential nematode-specific proteins in C. elegans. VHA-19 satisfied the criteria of the screen because it had less than 30% sequence identity over 150 amino acids to any mammalian proteins; it had 30% or greater sequence identity to predicted proteins from nematode parasites; and had a reported maternal sterile and lethal phenotype when gene expression was silenced by RNA interference (RNAi) [3,4,5]. The reproductive system of the C. elegans hermaphrodite consists of two U-shaped gonad arms that each terminate with a spermatheca, connecting to a central uterus. Oocytes and spermatozoa are generated from the primordial germ cell, which resides at the distal end of each gonad arm and proliferates by mitosis. Male C. elegans occur; they exclusively produce sperm and are capable of mating with hermaphrodite C. elegans. Male sperm are used preferentially [6,7]
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