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Cell Mol Neurobiol,
2016]
Cilia are sensory organelles that protrude from cell surfaces to monitor the surrounding environment. In addition to its role as sensory receiver, the cilium also releases extracellular vesicles (EVs). The release of sub-micron sized EVs is a conserved form of intercellular communication used by all three kingdoms of life. These extracellular organelles play important roles in both short and long range signaling between donor and target cells and may coordinate systemic responses within an organism in normal and diseased states. EV shedding from ciliated cells and EV-cilia interactions are evolutionarily conserved phenomena, yet remarkably little is known about the relationship between the cilia and EVs and the fundamental biology of EVs. Studies in the model organisms Chlamydomonas and Caenorhabditis elegans have begun to shed light on ciliary EVs. Chlamydomonas EVs are shed from tips of flagella and are bioactive. Caenorhabditis elegans EVs are shed and released by ciliated sensory neurons in an intraflagellar transport-dependent manner. Caenorhabditis elegans EVs play a role in modulating animal-to-animal communication, and this EV bioactivity is dependent on EV cargo content. Some ciliary pathologies, or ciliopathies, are associated with abnormal EV shedding or with abnormal cilia-EV interactions. Until the 21st century, both cilia and EVs were ignored as vestigial or cellular junk. As research interest in these two organelles continues to gain momentum, we envision a new field of cell biology emerging. Here, we propose that the cilium is a dedicated organelle for EV biogenesis and EV reception. We will also discuss possible mechanisms by which EVs exert bioactivity and explain how what is learned in model organisms regarding EV biogenesis and function may provide insight to human ciliopathies.
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Genetics,
2024]
Extracellular vesicles (EVs) encompass a diverse array of membrane-bound organelles released outside cells in response to developmental and physiological cell needs. EVs play important roles in remodeling the shape and content of differentiating cells and can rescue damaged cells from toxic or dysfunctional content. EVs can send signals and transfer metabolites between tissues and organisms to regulate development, respond to stress or tissue damage, or alter mating behaviors. While many EV functions have been uncovered by characterizing ex vivo EVs isolated from body fluids and cultured cells, research using the nematode Caenorhabditis elegans has provided insights into the in vivo functions, biogenesis, and uptake pathways. The C. elegans EV field has also developed methods to analyze endogenous EVs within the organismal context of development and adult physiology in free-living, behaving animals. In this review, we summarize major themes that have emerged for C. elegans EVs and their relevance to human health and disease. We also highlight the diversity of biogenesis mechanisms, locations, and functions of worm EVs and discuss open questions and unexplored topics tenable in C. elegans, given the nematode model is ideal for light and electron microscopy, genetic screens, genome engineering, and high-throughput omics.
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Dev Neurobiol,
2020]
Cilia are microtubule-based organelles that display diversity in morphology, ultrastructure, protein composition, and function. The ciliary microtubules of C. elegans sensory neurons exemplify this diversity and provide a paradigm to understand mechanisms driving ciliary specialization. Only a subset of ciliated neurons in C. elegans are specialized to make and release bioactive extracellular vesicles (EVs) into the environment. The cilia of extracellular vesicle releasing neurons have distinct axonemal features and specialized intraflagellar transport that are important for releasing EVs. In this review, we discuss the role of the tubulin code in the specialization of microtubules in cilia of EV releasing neurons.
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Essays Biochem,
2018]
In this short review, we will focus on the uniqueness of ciliary extracellular vesicles (EVs). In particular, we will review what has been learned regarding EVs produced by cilia of model organisms. Model systems including <i>Chlamydomonas, Caenorhabditis elegans</i>, and mouse revealed the fundamental biology of cilia and flagella and provide a paradigm to understand the roles of cilia and flagella in human development, health, and disease. Likewise, we propose that general principles learned from model systems regarding ciliary EV biogenesis and functions may provide a framework to explore the roles of ciliary EVs in human development, health, and disease.
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J Mol Biol,
2015]
Maf1 was first identified in yeast, and studies in metazoans have primarily focused on examining its role in the repression of transcription that is dependent on RNA polymerase III. Recent work has revealed a novel and conserved function for Maf1 in the maintenance of intracellular lipid pools in Caenorhabditis elegans, mice, and cancer cell lines. Although additional Maf1 targets are likely, they have not been identified, and these recent findings begin to define specific activities for Maf1 in multicellular organisms beyond the regulation of RNA polymerase III transcription and suggest that Maf1 plays a more diverse role in organismal physiology. We will discuss these newly defined physiological roles of Maf1 that point to its placement as an important new player in lipid metabolism with implications in human metabolic diseases such as obesity and cancer, which display prominent defects in lipid homeostasis.
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Cell,
2001]
In 1998, The C. elegans Sequencing Consortium (1998) announced the essentially complete Caenorhabditis elegans genomic sequence, setting a high standard for sequencing multicellular genomes. As of April 2001, the C. elegans genome, including repetitive regions, is >99.6% complete with sequence equivalent to what many genome projects call phase III. How has this changed the lives of C. elegans researchers, and our view of the worm?
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Dev Dyn,
2010]
We review recent studies that have advanced our understanding of the molecular mechanisms regulating transcription in the nematode C. elegans. Topics covered include: (i) general properties of C. elegans promoters; (ii) transcription factors and transcription factor combinations involved in cell fate specification and cell differentiation; (iii) new roles for general transcription factors; (iv) nucleosome positioning in C. elegans "chromatin"; and (v) some characteristics of histone variants and histone modifications and their possible roles in controlling C. elegans transcription.
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Biochim Biophys Acta,
2018]
As a master regulator of transcription by RNA polymerase (Pol) III, Maf1 represses the synthesis of highly abundant non-coding RNAs as anabolic signals dissipate, as the quality or quantity of nutrients decreases, and under a wide range of cellular and environmental stress conditions. Thus, Maf1 responds to changes in cell physiology to conserve metabolic energy and to help maintain appropriate levels of tRNAs and other essential non-coding RNAs. Studies in different model organisms and cell-based systems show that perturbations of Maf1 can also impact cell physiology and metabolism. These effects are mediated by changes in Pol III transcription and/or by effects of Maf1 on the expression of select Pol II-transcribed genes. Maf1 phenotypes can vary between different systems and are sometimes conflicting as in comparisons between Maf1 KO mice and cultured mammalian cells. These studies are reviewed in an effort to better appreciate the relationship between Maf1 function and cell physiology. This article is part of a Special Issue entitled: SI: Regulation of tRNA synthesis and modification in physiological conditions and disease edited by Dr. Boguta Magdalena.
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Canadian Journal of Zoology,
1988]
Nematodes have a number of biological attributes that make them amenable for molecular studies. In our laboratory, attention has focused on (i) determining the polypeptide composition of cuticles, (ii) using monoclonal antibodies to identify epitopes among the cuticular proteins, (iii) visualizing the sites of collagenous components within the cuticle of Ascaris by immunolocalization, and (iv) sequencing a moderately repetitive DNA element that is found, with extensive similarity, in the genomes of Ascaris and Panagrellus. The role of these and other molecular studies in understanding the biology of nematodes is discussed.
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Curr Opin Chem Biol,
2001]
In many species, double-stranded RNA can specifically and effectively silence genes. This newly discovered biological phenomenon, called RNA interference (RNAi), has practical implications for functional genomics. As shown by two recent reports, RNAi provides a rapid method to test the function of genes in the nematode Caenorhabditis elegans; most of the genes on C. elegans chromosome I and III have now been tested for RNAi phenotypes. The results validate RNAi as a powerful functional genomics tool for C. elegans, and point the way for similar large-scale studies in other species.