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[
WormBook,
2008]
The role of neuropeptides in modulating behavior is slowly being elucidated. With the sequencing of the C. elegans genome, the extent of the neuropeptide genes in C. elegans can be determined. To date, 113 neuropeptide genes encoding over 250 distinct neuropeptides have been identified. Of these, 40 genes encode insulin-like peptides, 31 genes encode FMRFamide-related peptides, and 42 genes encode non-insulin, non-FMRFamide-related neuropeptides. As in other systems, C. elegans neuropeptides are derived from precursor molecules that must be post-translationally processed to yield the active peptides. These precursor molecules contain a single peptide, multiple copies of a single peptide, multiple distinct peptides, or any combination thereof. The neuropeptide genes are expressed extensively throughout the nervous system, including in sensory, motor, and interneurons. In addition, some of the genes are also expressed in non-neuronal tissues, such as the somatic gonad, intestine, and vulval hypodermis. To address the effects of neuropeptides on C. elegans behavior, animals in which the different neuropeptide genes are inactivated or overexpressed are being isolated. In a complementary approach the receptors to which the neuropeptides bind are also being identified and examined. Among the knockout animals analyzed thus far, defects in locomotion, dauer formation, egg laying, ethanol response, and social behavior have been reported. These data suggest that neuropeptides have a modulatory role in many, if not all, behaviors in C. elegans.
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[
Adv Exp Med Biol,
2010]
Nematode neuropeptide systems comprise an exceptionally complex array of approximately 250 peptidic signaling molecules that operate within a structurally simple nervous system of approximately 300 neurons. A relatively complete picture of the neuropeptide complement is available for Caenorhabditis elegans, with 30 flp, 38 ins and 43 nlp genes having been documented; accumulating evidence indicates similar complexity in parasitic nematodes from clades I, III, IV and V. In contrast, the picture for parasitic platyhelminths is less clear, with the limited peptide sequence data available providing concrete evidence for only FMRFamide-like peptide (FLP) and neuropeptide F (NPF) signaling systems, each of which only comprises one or two peptides. With the completion of the Schmidtea meditteranea and Schistosoma mansoni genome projects and expressed sequence tag datasets for other flatworm parasites becoming available, the time is ripe for a detailed reanalysis ofneuropeptide signalingin flatworms. Although the actual neuropeptides provide limited obvious value as targets for chemotherapeutic-based control strategies, they do highlight the signaling systems present in these helminths and provide tools for the discovery of more amenable targets such as neuropeptide receptors or neuropeptide processing enzymes. Also, they offer opportunities to evaluate the potential of their associated signaling pathways as targets through RNA interference (RNAi)-based, target validation strategies. Currently, within both helminth phyla, theflp signaling systems appear to merit further investigation as they are intrinsically linked with motor function, a proven target for successful anti-parasitics; it is clear that some nematode NLPs also play a role in motor function and could have similar appeal. At this time, it is unclear if flatworm NPF and nematode INS peptides operate in pathways that have utility for parasite control. Clearly, RNAi-based validation could be a starting point for scoring potential target pathways within neuropeptide signaling for parasiticide discovery programs. Also, recent successes in the application of in planta-based RNAi control strategies for plant parasitic nematodes reveal a strategy whereby neuropeptide encoding genes could become targets for parasite control. The possibility of developing these approaches for the control of animal and human parasites is intriguing, but will require significant advances in the delivery of RNAi-triggers.
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[
1985]
Myosins from slime molds to brain cells show a remarkable commonality of general molecular properties. These characteristics include two globular domains or heads that contain ATPase and actin-binding sites and the fibrous, coiled-coil a-helical rod that interacts with other molecules in assembly. Two heavy chains (m.w. 200,000) contribute to both heads, whereas two kinds of light chains bind to each head. In this paper, we consider striated muscles and their myosins. The phylogenetically distant nematode body-wall muscles and rabbit fast skeletal muscles produce myosin heavy chains, with about 47% of the amino acid sequences in the heads and 37% of the amino acids in the rod being identical (Karn et al. 1984). Myosin heavy chains are therefore highly conserved proteins. Contrasting with the phylogenetic conservation of myosin structure and sequence is the diversity of supramolecular arrangements of myosin assemblies in striated muscles, the so-called thick filaments. The lengths of thick filaments range from 1.55 um in vertebrates, 2-4 um in insect flight muscles, 10 um in the nematode to 40 um in certain mollusks. The average diameters of these filaments range from about 15 nm in vertebrates, 20 nm in insects, 25 nm in nematodes to 50-100 nm in some molluscan muscles. The surface arrangements of the myosin heads also vary in these different species. The lattice arrangements between thick filaments and the interdigitating, actin-containing thin filaments differ in terms of symmetry and thick:thin stoichiometry between these muscles. It appears likely that other protein components of these muscles interact with the very similar myosins to produce this structural diversity. The relatively subtle differences between myosin isoforms may also be important in these interactions. We define isoform in the case of myosin, for example, as a protein that is defined as a myosin by biochemical criteria but that can be distinguished on the basis of intrinsic molecular structure from another myosin within the same organism. In this paper, we describe experiments suggesting that two genetically different isoforms of myosin play distinct roles in concert with other proteins during the assembly of thick filaments in
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[
1983]
The advantages of the free-living nematode Caenrohabditis elegans as a model for pharmacologic, toxicant and anthelmintic testing have become apparent to many companies, and the application of this organism as a primary screen for test compounds or toxic agents has expanded rapidly. It is appropriate to briefly summarize some of this nematode's qualities, to invoke an appreciation of this elegant system. As true of many invertebrate test organisms, C. elegans is small (about 1 mm X 40 u at maturity) and has a short life cycle: reproduction starts on day 3-4, ceases by day 14 and by day 25 it dies. Thus, for aging studies, all the symptoms of senescence are compressed into a short time period. In addition, this nematode has a small, fixed number of cells (about 830 at maturity) and differentiated organ systems: nervous, excretory, muscular, digestive and reproductive. The preceding characteristics are not unique in invertebrate model systems and their enumeration fails to explain the increasing popularity of C. elegans as a test organism. To understand this phenomenon several additional facts must be emphasized. First, the selection of C. elegans for detailed studies on the genetic control and regulation of behavior and developmental processes has fostered a wealth of knowledge on its neuroanatomy, cell lineages, biochemistry and behavior. There is now undoubtedly more accumulated knowledge on C. elegans than on any other multicellular creature. It is also the largest metazoan which can be continuously cultured on a chemically defined medium, and though most studies have proceeded on undefined media or in monoxenic culture (utilizing a bacterium as a food source), this property can be exploited for precise nutritional studies. In regard to aging studies, the question of relevance of aging in the nematode to that in mammals has been answered in respect to some parameters which characterize senescence in humans, and further study will define other features of aging which are common to all metazoa. In practical terms, this means that test which require 24-36 months to rear an aged rat for evaluation of a pharmaceutical, can potentially be accomplished in 21 days using the nematode. The paper emphasizes that the use of the C. elegans system as a primary screen for candidate compounds to intervene in the aging process can save time, effort and money, while