Identification of neuropeptide-like protein gene families in Caenorhabditiselegans 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, buccalin/drosulfakinin, orcokinin, and APGWamide neuropeptides (MGL/Famide, 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.

Figure 1

nlp genes encode putative neuropeptides. nlp genes are grouped into families (shaded); the family motif is listed in the first column along with the nlp gene name, ESTs, or cDNA designations. Only one yk EST (C. elegans EST project) and/or pHA cDNA clone (this paper) is listed even if multiple clones were identified. The second column indicates the chromosome, location (in map units), and cosmid designation. Predicted peptides are listed for each nlp gene in the third column. Peptides are predicted based on similarity within a nlp gene and putative mono- or dibasic endopeptidase cleavage. Putative peptides are listed sequentially for each nlp gene but identical putative peptides encoded by a nlp gene are listed only once; the number of times the putative peptide is repeated is indicated (2×, 3×). Predicted posttranslational modifications are not shown for individual predicted peptides. The last predicted nlp-21 peptide (parentheses) is differentially spliced. Cells expressing GFP from nlp gene reporter constructs are in the fourth column. Neurons/cells scored unequivocally by position and counterstaining: ASH, ASI, ASJ, ADL, ASK, AWB, PHA, PHB, HSN, BDU, spermatheca, vulval muscles, rectal gland cell, pharyngeal neurons, and hypoderm. Other classes of neurons were counted (head, tail, and lateral) but not always identified. Approximately 90% of cells expressing GFP in this figure are neurons. VNC, ventral nerve cord neurons; RVG, retrovesicular ganglion neurons. The last column lists the species and accession number for nlp gene family members in other species.