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The nkcc, kcc and abts genes code for members of the SLC superfamilies SLC12 and SLC4 (see Table 5). NKCC mediate Cl^– influx by coupling transport to the Na⁺ gradient, KCCs mediate Cl^– efflux by coupling transport to the K⁺ gradient, and ABTS transporters mediate Cl^– efflux and acid extrusion (Bellemer et al., 2011). As shown in Table 5, each of the SLC genes has multiple paralogs in the worm genome. The genes nkcc-1, kcc-2 and abts-1 have been shown to mediate these functions (Tanis et al., 2009; Bellemer et al., 2011). The direction of chloride flow through ligand-gated anionic channels like the GABA receptors (one representative shown here) is dictated principally by the ion concentration gradients produced by the three types of transporters. This figure is adapted from (Bellemer et al., 2011).

Ca²⁺ is represented by yellow dots, with its transport indicated by a yellow block arrow. Red arrows denote regulatory pathways. Several different cell types are important for fertilization, including sheath cells, spermatheca and the oocyte. The role of each of these cells has to be precisely coordinated in order for effective fertilization to occur. Hence, communication between cells is essential. Ca²⁺ signaling pathways have been shown to operate through discrete mechanisms in each cell to coordinate fertilization and assure the proper sequence of events. Inositol 1, 4, 5-trisphosphate (IP3), IP3 Receptor (IP3R), Voltage activated chloride channel (CLC), Oxidative stress responsive kinase 1/SPS1-related proline/alanine-rich kinase (OSR/SPAK), Protein phosphatase (PP), Ca²⁺ release-activated Ca²⁺ modulator 1 (Orai1), Stromal interaction molecule (Stim), Extracellular signal related kinase (ERK), ERK kinase (ERKK), Ca²⁺-calmodulin dependent kinase type II (CaMKII), Epidermal grown factor (EGF), EGF receptor, (EGFR), Ephrin receptor (EphR), Major sperm protein (MSP), N-methyl-D-aspartate receptor (NMDAR), phospholipase C (PLC), phosphatidylinositol 4,5-bisphosphate (PIP2), diacylglycerol (DAG), endoplasmic reticulum (ER).

Shading indicates whether the respective amine has been biochemically detected C. elegans (Pertel and Wilson, 1974; Sulston et al., 1975). Homologs for all biosynthetic enzymes exist in the C. elegans genome, but whether these homologs are utilized for the indicated biosynthetic steps is only known in the following cases: TH = tyrosine hydroxylase, encoded by cat-2; TDC = tyrosine decarboxylase, encoded by tdc-1; TBH = tyramine β-hydroxylase, encoded by tbh-1; TPH = tryptophan hydroxylase, encoded by tph-1; AAAD = aromatic amino acid decarboxylase, encoded by bas-1 for 5HT and dopamine biosynthesis; AANAT = aralkylamine N-acetyltransferase, encoded by anat-1; HIOMT = hydroxyindole-O-methyltransferase, encoded by homt-1. In other cases, indicated with “(?)”, the respective type of enzyme exists in the worm genome but its utilization is not clear: DBH (dopamine β-hydroxylase) function could be carried out by the very related TBH (tyrosine β-hydroxylase, encoded by tbh-1), but tbh-1 is not expressed in dopaminergic neurons and no norepinephrine (noradrenaline) or epinephrine (adrenaline) is readily detectable in C. elegans (Sulston et al., 1975). Aside from the characterized AAADs, bas-1 and tdc-1, there are several uncharacterized AAADs in the genome (hdl-1, hdl-2, basl-1, see text) that could serve to generate the trace amines tryptamine, histidine or phenylethylamine. In regard to PNMT (Phenylethanolamine N-methyltransferase), which generates epinephrine and synephrine in other species, there are three paralogous genes in the C. elegans genome (anmt-1 through anmt-3) which are equidistant to PNMT and its related enzymes indolethylamine N-methyltransferase (INMT) and nicotinamide N-methyltransferase (NNMT). INMT and NNMT are not involved in neurotransmitter metabolism but are generally thought to target xenobiotic compounds. The tyrosine-derived neuromodulators dopamine, norepinephrine and epinephrine are also referred to as “catecholamines” (benzene with two hydroxyl groups and a side-chain amine). Tryptophan-derived neuromodulators are also sometimes referred to as “indolamines” (benzene with nitrogen-containing pyrrol ring). In vertebrates, tyramine, octopamine, synephrine, tryptamine, histamine and phenylethylamine are generally considered trace amines.