trans

374 NEUROTRANSMITTERS
sensitivity to ivermectin, and the GluCl subunit
is sensitive to glutamate. Subsequently,
molecular genetic and cloning approaches
have led to the recognition of additional GluCl
subunits from C. elegans and parasitic nematodes
(summarized in Table 15.2).
GluCl subunit structure and ion channels
The presence of N-terminal cysteines in the
GluCl subunits and hydrophobicity analysis
suggest that GluCl subunits have similar motifs
common to all cys-loop ligand-gated channels.
The GluCl subunits have a second pair of
cysteine residues in the N-terminal extracellular
domain that are characteristic of this family
and the vertebrate glycine receptors. This
sequence similarity has led to the suggestion
that invertebrate GluCls are in fact orthologous
(connected) to the vertebrate glycine
receptor subunits. It is assumed that five GluCl
subunits come together, as do the subunits of
the nAChRs, to produce the GluCl ion channel,
but the stoichiometric arrangement has
not been determined for any native receptor.
GluCl1 and GluCl subunits may form
homo-oligomers (five identical subunits) to
form receptor ion channels as well as heterooligomers
(five subunits not identical) to form
channels when expressed in Xenopus oocytes.
GluCl subunits
In C. elegans, a family of genes encodes
-type subunits: glc-1 encodes the subunit
GluCl1, avr-15 encodes GluCl2 subunits,
avr-14 encodes GluCl3A and GluCl3B, and
glc-3 encodes a fourth GluCl. The avr-15
gene encodes two alternatively spliced channel
subunits that are present on pharyngeal
TABLE 15.2
Cloned glutamate-gated chloride channel subunits from Caenorhabditis elegans
Gene WormPep EMBL/Genbank Other name In vitro expression data 1 In vivo expression data 2
accession no. for subunit
glc-1 F11A5.10 U14524 GluCl Forms ivermectin-gated
channels
glc-2 F25F8.2 U14525 GluCl Forms glutamate-gated Pharyngeal muscle
channels
pm4 cells
glc-3 ZC317.3 AJ243914 Forms glutamate- and
ivermectin-gated channels
avr-14 B0207.12 U40573 GluCl3A AVR-14B forms glutamate- Multiple neurons in
(gbr-2) U41113 GluCl3B and ivermectin-gated the nerve ring. Ventral
channels
cord motor neurons
AVR-14A does not form and mechanosensory
functional channels
neurons
avr-15 T10G3.7 AJ000537 GluCl2A AVR-15L forms glutamate- Pharynx – pm4 & pm5
GluCl2B and ivermectin-gated cells. RME & RMG ring
channels
motor neurons, DA9 &
VA12 and other nerve
cord neurons
C27H5.5 U14635 Does not form functional
channels
1 Expression in Xenopus oocytes.
2 Reporter gene data.
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS