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Ann N Y Acad Sci,
2000]
Aging and a limited life span are fundamental biological realities. Recent studies have demonstrated that longevity can be manipulated and have revealed molecular mechanisms underlying longevity control in the soil nematode Caenorhabditis elegans. Signals from both neurons and the gonad appear to negatively regulate longevity. One tissue-specific signal involves an insulin-like phosphatidylinositol 3-OH kinase pathway, dependent upon the DAF-16 forkhead transcription factor. These signals regulate mechanisms determining longevity that include the OLD-1 (formerly referred to as TKR-1) receptor tyrosine kinase. Interestingly, increased resistance to environmental stress shows a strong correlation with life extension.
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Adv Exp Med Biol,
2013]
The oocyte-to-embryo transition refers to the process whereby a fully grown, relatively quiescent oocyte undergoes maturation, fertilization, and is converted into a developmentally active, mitotically dividing embryo, arguably one of the most dramatic transitions in biology. This transition occurs very rapidly in Caenorhabditis elegans, with fertilization of a new oocyte occurring every 23 min and the first mitotic division occurring 45 min later. Molecular events regulating this transition must be very precisely timed. This chapter reviews our current understanding of the coordinated temporal regulation of different events during this transition. We divide the oocyte-to-embryo transition into a number of component processes, which are coordinated primarily through the MBK-2 kinase, whose activation is intimately tied to completion of meiosis, and the OMA-1/OMA-2 proteins, whose expression and functions span multiple processes during this transition. The oocyte-to-embryo transition occurs in the absence of de novo transcription, and all the factors required for the process, whether mRNA or protein, are already present within the oocyte. Therefore, all regulation of this transition is posttranscriptional. The combination of asymmetric partitioning of maternal factors, protein modification-mediated functional switching, protein degradation, and highly regulated translational repression ensure a smooth oocyte-to-embryo transition. We will highlight protein degradation and translational repression, two posttranscriptional processes which play particularly critical roles in this transition.
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Trends Genet,
2018]
Any adult who has tried to take up the piano or learn a new language is faced with the sobering realization that acquiring such skills is more challenging as an adult than as a child. Neuronal plasticity, or the malleability of brain circuits, declines with age. Young neurons tend to be more adaptable and can alter the size and strength of their connections more readily than can old neurons. Myriad circuit- and synapse-level mechanisms that shape plasticity have been identified. Yet, molecular mechanisms setting the overall competence of young neurons for distinct forms of plasticity remain largely obscure. Recent studies indicate evolutionarily conserved roles for FoxO proteins in establishing the capacity for cell-fate, morphological, and synaptic plasticity in neurons.
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Exp Gerontol,
2006]
In Caenorhabditis elegans, the insulin/IGF-1 signaling pathway controls many biological processes such as life span, fat storage, dauer diapause, reproduction and stress response . This pathway is comprised of many genes including the insulin/IGF-1 receptor (DAF-2) that signals through a conserved PI 3-kinase/AKT pathway and ultimately down-regulates DAF-16, a forkhead transcription factor (FOXO). DAF-16 also receives input from several other pathways that regulate life span such as the germline and the JNK pathway [Hsin, H., Kenyon, C., 1999. Signals from the reproductive system regulate the lifespan of C. elegans. Nature 399, 362-366; Oh, S.W., Mukhopadhyay, A., Svrzikapa, N., Jiang, F., Davis, R.J., Tissenbaum, H.A., 2005. JNK regulates lifespan in Caenorhabditis elegans by modulating nuclear translocation of forkhead transcription factor/DAF-16. Proc. Natl. Acad. Sci. USA 102, 4494-4499]. Therefore, DAF-16 integrates signals from multiple pathways and regulates its downstream target genes to control diverse processes. Here, we discuss the signals to and from DAF-16, with a focus on life span regulation.
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Wiley Interdiscip Rev Dev Biol,
2014]
The Caenorhabditis elegans pharynx is a rhythmically pumping organ composed initially of 80 cells that, through fusions, amount to 62 cells in the adult worm. During the first 100 min of development, most future pharyngeal cells are born and gather into a double-plate primordium surrounded by a basal lamina. All pharyngeal cells express the transcription factor PHA-4, of which the concentration increases throughout development, triggering a sequential activation of genes with promoters responding differentially to PHA-4 protein levels. The oblong-shaped pharyngeal primordium becomes polarized, many cells taking on wedge shapes with their narrow ends toward the center, hence forming an epithelial cyst. The primordium then elongates, and reorientations of the cells at the anterior and posterior ends form the mouth and pharyngeal-intestinal openings, respectively. The 20 pharyngeal neurons establish complex but reproducible trajectories using 'fishing line' and growth cone-driven mechanisms, and the gland cells also similarly develop their processes. The genetics behind many fate decisions and morphogenetic processes are being elucidated, and reveal the pharynx to be a fruitful model for developmental biologists.
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Mol Neurobiol,
2007]
The nematode Caenorhabditis elegans is an excellent model organism to study biological processes relevant to a wide variety of human and rodent disease systems. Previous studies have suggested that mutants of the insulin/insulin-like growth factor-1 pathway show life extension and increased stress resistance in various species, including C. elegans, the fruit fly, and the mouse. It has recently been shown that the life-extending mutants, including the
age-1 phosphatidylinositol- 3 OH kinase mutants and the
daf-2 insulin-like receptor mutants, display improvement in a type of associative learning behavior called thermotaxis learning behavior. The
age-1 mutant shows a dramatic threefold extension of the health-span that ensures thermotaxis learning behavior, suggesting strong neuroprotective actions during aging. The
age-1 and
daf-2 mutants show resistance to multiple forms of stress and upregulates the genes involved in reactive oxygen species scavenging, heat shock, and P450 drug-detoxification. The life-extending mutants may confer resistance to various stress and diseases in neurons. Therefore, C. elegans provides an emerging system for the prevention of age-related deficits in the nervous system and in learning behaviors. This article discusses the aging of learning and memory and the neuroprotection effects of life-extending mutants on learning behaviors.
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Philos Trans R Soc Lond B Biol Sci,
2018]
Dynamic patterning of specific proteins is essential for the spatio-temporal regulation of many important intracellular processes in prokaryotes, eukaryotes and multicellular organisms. The emergence of patterns generated by interactions of diffusing proteins is a paradigmatic example for self-organization. In this article, we review quantitative models for intracellular Min protein patterns in <i>Escherichia coli</i>, Cdc42 polarization in <i>Saccharomyces cerevisiae</i> and the bipolar PAR protein patterns found in <i>Caenorhabditis elegans</i> By analysing the molecular processes driving these systems we derive a theoretical perspective on general principles underlying self-organized pattern formation. We argue that intracellular pattern formation is not captured by concepts such as 'activators', 'inhibitors' or 'substrate depletion'. Instead, intracellular pattern formation is based on the redistribution of proteins by cytosolic diffusion, and the cycling of proteins between distinct conformational states. Therefore, mass-conserving reaction-diffusion equations provide the most appropriate framework to study intracellular pattern formation. We conclude that directed transport, e.g. cytosolic diffusion along an actively maintained cytosolic gradient, is the key process underlying pattern formation. Thus the basic principle of self-organization is the establishment and maintenance of directed transport by intracellular protein dynamics.This article is part of the theme issue 'Self-organization in cell biology'.
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Proteomics,
2016]
Galactose1-4fucose (Gal1-4Fuc), a unique disaccharide unit found only on the N-glycans of Protostomia, has been intensively studied, particularly in Nematoda. Gal1-4Fuc attached to the 6-OH of the innermost GlcNAc of N-glycans has been identified as an endogenous target recognized by Caenorhabditis elegans galectin LEC-6 and might function as an endogenous ligand for other galectins as well. Interactions between galectins and N-glycans might be subject to fine-tuning through modifications of the penultimate GlcNAc and the Gal1-4Fuc unit. Similar fine-tuning is also observable in vertebrate galectins, although their major recognition unit is a Gal1-4GlcNAc. In Protostomia, it can be postulated that glycan binding proteins and their ligands have co-evolved; however, epitopes such as Gal1-4Fuc were then hijacked as targets by other organisms. Fungal (Coprinopsis cinerea) galectin 2, CGL2, binds the Gal1-4Fuc on Caenorhabditis elegans glycans to exert its nematotoxicity. Some human and mouse galectins bind to synthesized Gal1-4Fuc; as some parasitic nematodes express this motif, its recognition by mammalian galectins could hypothetically be involved in host defense, similar to fungal CGL2. In this review, we discuss the Gal1-4Fuc unit in Protostomia as a possible equivalent for the Gal1-4GlcNAc unit in vertebrates and a potential non-self glycomarker useful for pathogen recognition. This article is protected by copyright. All rights reserved.
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Exp Biol Med (Maywood),
2008]
5''-AMP-activated protein kinase (AMPK) has been called "the metabolic master switch" because of its central role in regulating fuel homeostasis. AMPK, a heterotrimeric serine/threonine protein kinase composed of alpha, beta, and gamma subunits, is activated by upstream kinases and by 5''-AMP in response to various nutritional and stress signals. Downstream effects include regulation of metabolism, protein synthesis, cell growth, and mediation of the actions of a number of hormones, including leptin. However, AMPK research represents a young and growing field; hence, there are many unanswered questions regarding the control and action of AMPK. This review presents evidence for the existence of AMPK signaling pathways in Caenorhabditis elegans, a genetically tractable model organism that has yet to be fully exploited to elucidate AMPK signaling mechanisms.
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Elife,
2015]
The roundworm Caenorhabditis elegans has risen to the status of a top model organism for biological research in the last fifty years. Among laboratory animals, this tiny nematode is one of the simplest and easiest organisms to handle. And its life outside the laboratory is beginning to be unveiled. Like other model organisms, C. elegans has a boom-and-bust lifestyle. It feasts on ephemeral bacterial blooms in decomposing fruits and stems. After resource depletion, its young larvae enter a migratory diapause stage, called the dauer. Organisms known to be associated with C. elegans include migration vectors (such as snails, slugs and isopods) and pathogens (such as microsporidia, fungi, bacteria and viruses). By deepening our understanding of the natural history of C. elegans, we establish a broader context and improved tools for studying its biology.