[
1985]
Expression of the vitellogenin genes is restricted to the intestine of adult hermaphrodite C. elegans. In order to identify potential cis-acting elements involved in this developmental regualtion, we have sequenced the regions surrounding the 5' ends of five of the six members of this gene family. In addition, we have sequenced several of the promoters from the homologous genes from the related species C. briggsae. Although the various promoters are largely diverged from one another, we have discovered two potential regulatory sequences within the first 250 bp upstream of each of the genes. The first, TGTCAAT, occurs eight times as a perfect heptamer upstream of the five C. elegans genes, at least once per promoter. Allowing a 1 bp mismatch, the element is found in both orientations a total of 27 times, four to six timer per promoter. It is present preferentially at two locations: just upstream of the TATA box and, in the opposite orientation, at position -180. The second sequence, CTGATAA, is also present as a perfect heptamer in a restricted region of each promoter: near position -135. Remarkably, this sequence is also found upstream of the vitellogenin genes of vertebrates. Both sequences have been conserved in the C. briggsae promoters. We hypothesize that these two sequences are involved in the sex-, tissue-, and stage-specific expression of the vitellogenin genes.
[
1989]
Transposable elements have recently been described in several species: Caenorhabditis elegans, Caenorhabditis briggsae, Ascaris lumbricoides, and Panagrellus redivivus. Because of the intense interest in C. elegans as an experimental organism for developmental genetic studies and the availability of sophisticated genetics, most is know about transposons in this species. This review focuses principally on Tc1 (Tc=transposon) of C. elegans, the best understood element in nematodes. Other elements in C. elegans and also elements in other species of nematodes will be briefly surveyed. The interested reader should also see two recent related reviews. The genome of C. elegans is 8 x 10(7) base pairs (bp) in extent, the smallest known for any metazoan. There are six chromosomes per haploid set, and about 83% of C. elegans DNA behaves as single-copy sequence in renaturation experiments. The repeated sequences are of several types, including functional genes, inverted or "foldback" sequences, and short repeated sequences of a few hundred nucleotides. The global arrangment of these short repeats is of the "short-period-interspersion" or "Xenopus" pattern. Some of the repetitive sequences consist of transposable elements, and at least five distinct families have been identified in C. elegans, Tc1 through Tc5. The sequence of one Tc1 element has been determined and shows that Tc1 resembles bacterial insertion sequence elements with terminal inverted repeats and a central open reading frame. The complete sequences for any members of the other transposon families have not been determined, but the data suggest that Tc2, Tc3, and Tc5 are also insertion sequence-like in structure and that Tc4 is foldbacklike in structure. No "retrotransposon-like" elements have been identified in C. elegans, although such elements have been described in A.
[
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
[
2017]
An organism's health depends on the integrity of molecular and biochemical networks responsible for ensuring homeostasis within its cells and tissues. However, upon aging, a progressive failure in the maintenance of this homeostatic balance occurs in response to various insults, allowing the accumulation of damage, the physiological decline of individual tissues, and susceptibility to diseases. Despite the complex nature of the aging process, simple genetic and environmental alterations can cause an increase in healthy lifespan or "healthspan" in laboratory model organisms. Genetic manipulations of model organisms including yeast, worms, flies, and mice have revealed signaling elements involved in DNA damage, stem cells maintenance, proteostasis, energy, and oxidative metabolism (Riera et al., 2016). However, one of the most intriguing discoveries made in these models resides in the ability of environmental factors to profoundly alter the aging process by remodeling some of the genetic programs mentioned above (Riera and Dillin, 2016). The first line of evidence that an external cue could powerfully regulate longevity was obtained by performing dietary restriction in rodents, a reduction in food intake without malnutrition. Dietary restriction is the most robust intervention to increase lifespan in model organisms including rodents and primates, and delays the emergence of age-related diseases (Mair and Dillin, 2008). How dietary restriction extends lifespan remains an open question, but decades of research are evidencing molecular pathways embedded in the response to reduce energy availability, resulting in the emergence of an altered metabolic state that promotes health and longevity. Nonetheless, the discovery of dietary restriction opened a new avenue of research in the aging field, and in particular in the understanding of how animals deal with fluctuating energy levels in their natural environment, and how their longevity is affected by such factors. This is particularly relevant for the nematode Caenorhabditis elegans, which survives in a changing environment and must be able to coordinate energy-demanding processes including basal cellular functions, growth, reproduction, and physical activity with available external resources. In order to sense their environment, C. elegans possess ciliated sensory neurons located primarily in sensory organs in the head and tail regions. Cilia function as sensory receptors, expressing many G protein-coupled receptors (GPCRs) and transient receptor potential (TRP) channels, and mutants with defective sensory cilia have impaired sensory perception (Bargmann, 2006). Cilia are membrane-bound microtubule-based structures and in C. elegans are only found at the dendritic endings of sensory neurons. Sensory neurons provide nematodes with a remarkable form of developmental plasticity, allowing them to assess food availability, temperature, and crowding information (worm density) in order to arrest their development if required, thus forming long-lived and stress-resistant dauer larvae (Bargmann, 2006; Golden and Riddle, 1982). When favorable times return, worms assess the same cues to recover and resume normal development. As the entry and exit of the dauer larval stage suggest, worm sensory neurons truly function as neuroendocrine organs, being implicated in many physiological functions in addition to their behavioral role (Bargmann, 2006). Much information on these neurons has been gathered from laser ablation experiments and analysis of mutants presenting defects in sensory cilia. A seminal discovery in the aging field was achieved when the laboratory of Cynthia Kenyon showed in 1999 that mutations that cause various defects in cilia formation, including the absence of cilia, deletion of middle and distal segments, or impair chemosensory signal transduction increase longevity profoundly (Apfeld and Kenyon, 1999). Later, this group also demonstrated that laser ablation of specific pairs of gustatory and olfactory chemosensory neurons was sufficient to extend lifespan (Alcedo and Kenyon, 2004). What is the role of TRP channels in modulating these neuroendocrine processes, and what kind of stimuli are these receptors detecting to control aging? This chapter summarizes relevant discoveries that clarify some of the roles of TRP channels in the aging process.