Gene expression and function of FMRFamide-related neuropeptides in the snail Lymnaea

FMRFamide and a large family of related peptides (FaRPs) have been identified in every major metazoan phylum examined, including chordates. In the pulmonate snail Lymnaea this family of neuropeptides is encoded by a five-exon locus that is subject to alternative splicing. The two alternative mRNA transcripts are expressed in the CNS in a mutually exclusive manner at the single cell level, resulting in the differential distribution of the distinct sets of FaRPs that they encode in defined neuronal networks. Biochemical peptide purification, single-cell analysis by mass spectroscopy, and immunocytochemistry have led to an understanding of the post-translational processing patterns of the two alternative precursor proteins and identified at least 12 known and novel peptides contained in neuronal networks involved in cardiorespiration, penial control and withdrawal response. The pharmacological actions of single or co-expressed peptides are beginning to emerge for the cardiorespiratory network and its central and peripheral targets. Peptides derived from protein precursor 1 and contained in the heart excitatory central motoneurons E(he) have distinct functions and also act in concert in cardiac regulation, based on their unique effects on heartbeat and their differential stimulatory effects on second messenger pathways. Precursor-2 derived peptides, contained in the Visceral White Interneuron, a key neuron of the cardiorespiratory network, have mostly inhibitory effects on the VWI's central postsynaptic target neurons but with some of the peptides also exhibiting excitatory effects on the same cells.