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regulation in C. elegans. For example, 22 genes
encoding Na channels in the degenerin (e.g.
deg-1, after ‘degeneration’) and mechanosensory
(e.g. mec-4 and mec-10) families have been
identified. In other organisms, related channels
form amiloride-sensitive Na channels in
Na -resorbing epithelial cells. In vertebrates,
they are targets for aldosterone in apical membranes
of kidney and intestinal epithelial cells.
Evidence for their involvement in volume- or
osmoregulation in C. elegans comes from studies
showing that null mutations at these genes
lead to enhanced Na flux, swelling and eventual
degeneration of mechanosensory cells in
the amphids. If members of this channel family
are expressed in the intestine, hypodermis or
tubular system in nematodes, they would be
positioned to affect ion and water movement
across these surfaces.
Other channels in nematode surface membranes
probably contribute to volume regulation,
including those that regulate flux of other
inorganic ions such as Cl and K . In vertebrates,
volume regulation is partially regulated
by CLC-2, a low conductance Cl channel that is
activated by both swelling and acidosis. This
channel is different from a Ca 2 -activated
organic anion-conducting Cl channel that has
been identified in hypodermal membranes
(described below). Two other Cl channels present
in vertebrates, with homologs in C. elegans,
are activated by swelling: CLC-3, which conducts
organic anions such as acetate and gluconate,
and VRAC (volume regulated anion
channel). Conductance of other, uncharged
organic osmolytes by VRAC is greater than for
Cl by a factor of at least 6. In addition, two
genes encoding K–Cl cotransporters have been
identified in C. elegans. In mammals, K–Cl cotransporters
typically function to balance water
flux across the opposite faces of epithelial cells
to maintain cell volume. It is tempting to speculate
that the nematode homologs could function
in osmoregulation or in regulation of turgor
pressure. Tissue localization and dsRNAi or
gene deletion could be used to test that concept.
Nematodes may also adjust osmotic pressure
by regulating the rate of transmural organic
acid excretion (see below), or the intracellular
concentrations of other organic osmolytes.
During periods of dehydration and rehydration,
for example, cuticle transport may function in
concert with metabolism, including production
of organic protectants, such as glycerol
and trehalose, to maintain water balance.
Trehalose is abundant in several parasitic
species and in all life-cycle stages of C. elegans.
Trehalose synthesis is catalyzed by trehalose
6-phosphate synthase and trehalose 6-phosphate
phosphatase, and it is metabolized by
trehalase. These enzymes have been cloned in
C. elegans. Since vertebrates do not synthesize or
utilize trehalose, nematode enzymes involved
with its processing may be good anthelmintic
targets.
Excretion
It is important to distinguish excretion from
secretion. These two processes have often been
considered together in the parasitology literature,
under the combined heading ‘excretory/
secretory products’. We consider excretion to
mean the removal of unusable or unnecessary
material. Secretion is the active release of molecules
that convey a survival advantage to the
organism. Nematodes secrete an array of proteins
(and possibly non-protein molecules) that
assist in nutrient acquisition, defense against
host responses and manipulation of the host
environment. We focus discussion here on
processes involved in excretion only. Animals
typically excrete two kinds of products. Ingested
material that is not digested is shed from the
intestine as solid material called feces. In
higher organisms, the soluble waste products
of intermediary metabolism and catabolism
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS