C. elegans flavin-containing monooxygenase-4 is essential for osmoregulation in hypotonic stress

Studies in Caenorhabditiseleganshave revealed osmoregulatory systems engaged when worms experience hypertonic conditions, but less is known about measures employed when faced with hypotonic stress. Inactivation offmo-4, which encodes flavin-containing monooxygenase-4, results in dramatic hypoosmotic hypersensitivity; worms are unable to prevent overwhelming water influx and swell rapidly, finally rupturing due to high internal hydrostatic pressure.fmo-4is expressed prominently in hypodermis, duct and pore cells but is excluded from the excretory cell. Thus, FMO-4 plays a crucial osmoregulatory role by promoting clearance of excess water that enters during hypotonicity, perhaps by synthesizing an osmolyte that acts to establish an osmotic gradient from excretory cell to duct and pore cells.C. elegansFMO-4 contains a C-terminal extension conserved in all nematode FMO-4s. The coincidently numbered human FMO4 also contains an extended C-terminus with features similar to those of FMO-4. Although these shared sequence characteristics suggest potential orthology, humanFMO4was unable to rescue thefmo-4osmoregulatory defect. Intriguingly, however, mammalianFMO4is expressed predominantly in the kidney - an appropriate site if it too is, or once was, involved in osmoregulation.