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NEUROTRANSMITTERS IN NEMATODES 383
Nematode FaRP genes
Twenty genes encoding 56 FaRPs have been
identified in C. elegans. Of these, 13 FaRPs have
been isolated. The C. elegans FaRP-encoding
genes have been named flp-1 to flp-20. Flp-1,
6, 8, 9, 13, 14 and 18 encode the
FaRPs that have been extracted from C. elegans.
Seven of the FaRP genes (in C. elegans and
A. suum) encode multiple copies of their peptides,
which is in marked contrast to the situation
in mammals. The FaRP-encoding genes
that have been found in vertebrates carry only
one copy of each peptide.
So far, one FaRP-encoding gene (afp-1) has
been identified in A. suum. It encodes six distinct
FaRPs with the same C-terminal sequence,
PGVLRFamide. This makes afp-1 similar to,
perhaps homologous with, flp-18. Of the
FaRPs encoded by afp-1, three have been isolated
from A. suum. The gene afp-1 has single
copies of each of the encoded peptides, like
flp-18. Alternative splicing occurs in the transcription
of afp-1, but unlike the process in
C. elegans, the alternative transcripts of afp-1
differ only in their untranslated regions (UTRs).
The reason for alternative transcripts that vary
in the UTRs only is not known; perhaps information
contained in the UTRs may control
gene expression by an unknown mechanism.
A directly-gated FaRP channel
FMRFamide, a molluscan cardioexcitatory peptide
and the original FaRP, directly gates a
sodium channel in the Helix C2 neuron. The
FMRFamide-gated sodium channel has been
cloned and expressed in Xenopus laevis oocytes.
Its pharmacology and channel characteristics
are similar to a superfamily of sodium channels,
although sequence identity is low. The
sodium channel superfamily is composed of
epithelial sodium channels and degenerins, and
has been named as the ENaCh/Deg superfamily.
FIGURE 15.18 PF4-activated single-channel currents
recorded from Ascaris somatic muscle. The
channels have conductance of 3 pS and are small in
amplitude.
The subunits of the FMRFamide-gated sodium
channel show only 16% homology with the
epithelial sodium channels and 13% with the
degenerins. However, the protein structure of
all three types of subunit is similar, having
a large hydrophobic, membrane-spanning
domain at each end of an extracellular loop,
and one or two cysteine-rich regions. The
FMRFamide-gated sodium channel subunits
are arranged in groups of four, or tetramers, to
form the functional channel. The other superfamilies
of ligand-gated channels that have
been characterized to date do not share these
structural features. PF4 appears to directly
gate a small conductance 2–5 pS Cl channel
(Figure 15.18).
Diversity of FaRP receptors
It is clear that FaRPs are extensively involved
in nematode muscle control. In view of the
wide spectrum of functions mediated by FaRPs
in nematodes, corresponding variation in nematode
FaRP receptors would be predicted. The
mechanisms of action of nematode FaRPs
substantiate this prediction. Studies in other
invertebrates demonstrate a variety of FaRP
receptors linked to ion channels. It is likely
that a similar range of FaRP receptors exists in
nematodes, which would explain the range of
mechanisms of action that are already known.
BIOCHEMISTRY AND CELL BIOLOGY: HELMINTHS