Identification of neuropeptide-like protein gene families in Caenorhabditis elegans and other species

Abstract

Neuropeptides play critical roles in synaptic signaling in all nervous systems. Unlike classical neurotransmitters, peptidergic neurotransmitters are encoded as preproproteins that are posttranslationally processed to yield bioactive neuropeptides. To identify novel peptidergic neurotransmitters, the Caenorhabditis elegans genome was searched for predicted proteins with the structural hallmarks of neuropeptide preproproteins. Thirty-two C. elegans neuropeptide-like protein (nlp) genes were identified. The nlp genes define at least 11 families of putative neuropeptides with unique motifs; similar expressed sequence tags were identified in other invertebrate species for all 11 families. Six of these families are defined by putative bioactive motifs (FAFA, GGxYamide, MRxamide, LQFamide, LxDxamide, and GGARAF); the remaining five families are related to allatostatin, myomodulin, buccalin͞drosul-fakinin, orcokinin, and APGWamide neuropeptides (MGL͞Famide, FRPamide, MSFamide, GFxGF, and YGGWamide families, respectively). Most C. elegans nlp gene expression is in neurons. The C. elegans nlp genes and similar genes encoding putative neuropeptides in other species are likely to play diverse roles in nervous system function. C hemical signaling via neurotransmitters is critical for synaptic transmission of information between neurons. Neuropeptides are the most varied and numerous type of neurotransmitters. Invertebrate neuropeptides are thought primarily to modulate synaptic function of classical small-molecule neurotransmitters by means of seven transmembrane domain receptors. However, the recent identification of a FMRFamide-gated sodium channel from Helix lucorum suggests that they may also act as fast transmitters (1). In mammals, neuropeptides and their receptors are implicated in behaviors including feeding and sleep (2-5). Despite their clear roles in synaptic signaling and behavior, neuropeptide functions are still not understood.Biochemical isolation of neuropeptides has been relatively successful in several invertebrate systems, including Lymnaea stagnalis, Drosophila melanogaster, and Aplysia californica (6-8), and has led to the identification of several invertebrate neuropeptide families. In the nematode Caenorhabditis elegans, 23 FMRFamide-related proteins (FaRP) neuropeptide genes, designated flp-1 to flp-23 (FMRFamide-like proteins), have been identified (9). Only flp-1 has been characterized at the functional level. Animals lacking flp-1 have abnormal behavior, including uncoordinated movement and hyperactivity (10). The only other C. elegans non-flp neuropeptide genes that have been identified are the 37 insulin-like genes (11, 12).Dense-core synaptic vesicles are prevalent in presynaptic terminals of C. elegans neurons that are neither FaRP immunoreactive nor catecholaminergic (13), suggesting that nonFaRP neuropeptides are present. Additionally, about 130 genes encoding putative neuropeptide receptors were identified in the C. elegans genome (14). This large number of receptors is much higher than the...

Generation and modulation of chemosensory behaviors in C. elegans

“…1a,b), suggesting the possibility of cross-talk and feedback regulation of chemosensory function (discussed further below). Both electrical and chemical synapses are present, and individual chemosensory neurons also contain dense core vesicles and express neuropeptide genes [53, [59][60][61][62]. The major postsynaptic outputs of the chemosensory neurons are a few interneuron types, with each interneuron type receiving inputs from partly overlapping groups of chemosensory neurons [53] (Fig.…”

Behavioral plasticity in C. elegans: Paradigms, circuits, genes

“…In this regard, the genome again invites some further speculations: First, as mentioned above, C. elegans contains a large number of neuropeptides, more than 200 of which are readily recognizable (151 NLP peptides encoded by 32 nlp genes, Nathoo et al, 2001; 59 FLP proteins encoded by 22 flp genes, Li et al, 1999;37 insulinlike proteins, Pierce et al, 2001). Presumably many more await identification.…”

Fishing lines, time‐delayed guideposts, and other tricks used by developing pharyngeal neurons in Caenorhabditis elegans

“…However, in some nematode species, the M2 neurons are essential for anterior isthmus peristalsis (Chiang et al, 2006). Neurotransmitters produced by the M2 neurons include acetylcholine (Alfonso et al, 1993), the FMRFamide-related neuropeptides FLP-18 and FLP-21 (Rogers et al, 2003), and the neuropeptide-like proteins NLP-3 and NLP-13 (Nathoo et al, 2001).…”