posted on 2021-08-04, 17:39authored byLouise
E. Atkinson, Yang Liu, Fiona McKay, Elke Vandewyer, Charles Viau, Allister Irvine, Bruce A. Rosa, Zihui Li, Qingxiao Liang, Nikki J. Marks, Aaron G. Maule, Makedonka Mitreva, Isabel Beets, Lingjun Li, Angela Mousley
Neural circuit synaptic
connectivities (the connectome) provide
the anatomical foundation for our understanding of nematode nervous
system function. However, other nonsynaptic routes of communication
are known in invertebrates including extrasynaptic volume transmission
(EVT), which enables short- and/or long-range communication in the
absence of synaptic connections. Although EVT has been highlighted
as a facet of Caenorhabditis elegans neurosignaling,
no experimental evidence identifies body cavity fluid (pseudocoelomic
fluid; PCF) as a vehicle for either neuropeptide or biogenic amine
transmission. In the parasitic nematode Ascaris suum, FMRFamide-like peptides encoded on flp-18 potently
stimulate female reproductive organs but are expressed in cells that
are anatomically distant from the reproductive organ, with no known
synaptic connections to this tissue. Here we investigate nonsynaptic
neuropeptide signaling in nematodes mediated by the body cavity fluid.
Our data show that (i) A. suum PCF (As-PCF) contains
a catalog of neuropeptides including FMRFamide-like peptides and neuropeptide-like
proteins, (ii) the A. suum FMRFamide-like peptide
As-FLP-18A dominates the As-PCF peptidome, (iii) As-PCF potently modulates
nematode reproductive muscle function ex vivo, mirroring
the effects of synthetic FLP-18 peptides, (iv) As-PCF activates the C. elegans FLP-18 receptors NPR-4 and -5, (v) As-PCF alters C. elegans behavior, and (vi) FLP-18 and FLP-18 receptors
display pan-phylum distribution in nematodes. This study provides
the first direct experimental evidence to support an extrasynaptic
volume route for neuropeptide transmission in nematodes. These data
indicate nonsynaptic signaling within the nematode functional connectome
and are particularly pertinent to receptor deorphanization approaches
underpinning drug discovery programs for nematode pathogens.