The role of C. elegans stearoyl‐CoA desaturases in fat storage and energy homeostasis

Gene regulatory information can be inherited between generations in a phenomenon termed transgenerational epigenetic inheritance (TEI). While examples of TEI in many animals accumulate, the nematode Caenorhabditis elegans has proven particularly useful in investigating the underlying molecular mechanisms of this phenomenon. In C. elegans and other animals, the modification of histone proteins has emerged as a potential carrier and effector of transgenerational epigenetic information. In this review, we explore the contribution of histone modifications to TEI in C. elegans. We describe the role of repressive histone marks, histone methyltransferases, and associated chromatin factors in heritable gene silencing, and discuss recent developments and unanswered questions in how these factors integrate with other known TEI mechanisms. We also review the transgenerational effects of the manipulation of histone modifications on germline health and longevity.

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Centrosome Aurora A gradient ensures single polarity axis in C. elegans embryos

Biochemical Society Transactions ◽

10.1042/bst20200298 ◽

2020 ◽

Vol 48 (3) ◽

pp. 1243-1253 ◽

Cited By ~ 1

Author(s):

Sukriti Kapoor ◽

Sachin Kotak

Keyword(s):

Symmetry Breaking ◽

Cell Fate ◽

Cell Cortex ◽

Axis Formation ◽

Aurora A Kinase ◽

Aurora A ◽

C Elegans ◽

Cell Embryo ◽

Polarity Establishment

Cellular asymmetries are vital for generating cell fate diversity during development and in stem cells. In the newly fertilized Caenorhabditis elegans embryo, centrosomes are responsible for polarity establishment, i.e. anterior–posterior body axis formation. The signal for polarity originates from the centrosomes and is transmitted to the cell cortex, where it disassembles the actomyosin network. This event leads to symmetry breaking and the establishment of distinct domains of evolutionarily conserved PAR proteins. However, the identity of an essential component that localizes to the centrosomes and promotes symmetry breaking was unknown. Recent work has uncovered that the loss of Aurora A kinase (AIR-1 in C. elegans and hereafter referred to as Aurora A) in the one-cell embryo disrupts stereotypical actomyosin-based cortical flows that occur at the time of polarity establishment. This misregulation of actomyosin flow dynamics results in the occurrence of two polarity axes. Notably, the role of Aurora A in ensuring a single polarity axis is independent of its well-established function in centrosome maturation. The mechanism by which Aurora A directs symmetry breaking is likely through direct regulation of Rho-dependent contractility. In this mini-review, we will discuss the unconventional role of Aurora A kinase in polarity establishment in C. elegans embryos and propose a refined model of centrosome-dependent symmetry breaking.

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Characterization of Caenorhabditis elegans Homologs of the Down Syndrome Candidate Gene DYRK1A

Genetics ◽

10.1093/genetics/163.2.571 ◽

2003 ◽

Vol 163 (2) ◽

pp. 571-580 ◽

Cited By ~ 1

Author(s):

William B Raich ◽

Celine Moorman ◽

Clay O Lacefield ◽

Jonah Lehrer ◽

Dusan Bartsch ◽

...

Keyword(s):

Down Syndrome ◽

Caenorhabditis Elegans ◽

Trisomy 21 ◽

Gene Dosage ◽

Inducible Promoters ◽

C Elegans ◽

Dual Specificity ◽

Specificity Protein

Abstract The pathology of trisomy 21/Down syndrome includes cognitive and memory deficits. Increased expression of the dual-specificity protein kinase DYRK1A kinase (DYRK1A) appears to play a significant role in the neuropathology of Down syndrome. To shed light on the cellular role of DYRK1A and related genes we identified three DYRK/minibrain-like genes in the genome sequence of Caenorhabditis elegans, termed mbk-1, mbk-2, and hpk-1. We found these genes to be widely expressed and to localize to distinct subcellular compartments. We isolated deletion alleles in all three genes and show that loss of mbk-1, the gene most closely related to DYRK1A, causes no obvious defects, while another gene, mbk-2, is essential for viability. The overexpression of DYRK1A in Down syndrome led us to examine the effects of overexpression of its C. elegans ortholog mbk-1. We found that animals containing additional copies of the mbk-1 gene display behavioral defects in chemotaxis toward volatile chemoattractants and that the extent of these defects correlates with mbk-1 gene dosage. Using tissue-specific and inducible promoters, we show that additional copies of mbk-1 can impair olfaction cell-autonomously in mature, fully differentiated neurons and that this impairment is reversible. Our results suggest that increased gene dosage of human DYRK1A in trisomy 21 may disrupt the function of fully differentiated neurons and that this disruption is reversible.

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Syndecan Transmembrane Domain Specifically Regulates Downstream Signaling Events of the Transmembrane Receptor Cytoplasmic Domain

International Journal of Molecular Sciences ◽

10.3390/ijms22157918 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7918

Author(s):

Jisun Hwang ◽

Bohee Jang ◽

Ayoung Kim ◽

Yejin Lee ◽

Joonha Lee ◽

...

Keyword(s):

Transmembrane Domain ◽

Growth Factor Receptor ◽

Cytoplasmic Domain ◽

Nih3t3 Cells ◽

C Elegans ◽

Downstream Signaling ◽

Downstream Effectors ◽

Signaling Events

Despite the known importance of the transmembrane domain (TMD) of syndecan receptors in cell adhesion and signaling, the molecular basis for syndecan TMD function remains unknown. Using in vivo invertebrate models, we found that mammalian syndecan-2 rescued both the guidance defects in C. elegans hermaphrodite-specific neurons and the impaired development of the midline axons of Drosophila caused by the loss of endogenous syndecan. These compensatory effects, however, were reduced significantly when syndecan-2 dimerization-defective TMD mutants were introduced. To further investigate the role of the TMD, we generated a chimera, 2eTPC, comprising the TMD of syndecan-2 linked to the cytoplasmic domain of platelet-derived growth factor receptor (PDGFR). This chimera exhibited SDS-resistant dimer formation that was lost in the corresponding dimerization-defective syndecan-2 TMD mutant, 2eT(GL)PC. Moreover, 2eTPC specifically enhanced Tyr 579 and Tyr 857 phosphorylation in the PDGFR cytoplasmic domain, while the TMD mutant failed to support such phosphorylation. Finally, 2eTPC, but not 2eT(GL)PC, induced phosphorylation of Src and PI3 kinase (known downstream effectors of Tyr 579 phosphorylation) and promoted Src-mediated migration of NIH3T3 cells. Taken together, these data suggest that the TMD of a syndecan-2 specifically regulates receptor cytoplasmic domain function and subsequent downstream signaling events controlling cell behavior.

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Interactions between the WEE-1.3 kinase and the PAM-1 aminopeptidase in oocyte maturation and the early C. elegans embryo

G3 Genes|Genome|Genetics ◽

10.1093/g3journal/jkab063 ◽

2021 ◽

Author(s):

Dorothy Benton ◽

Eva C Jaeger ◽

Arielle Kilner ◽

Ashley Kimble ◽

Josh Lowry ◽

...

Keyword(s):

Missense Mutation ◽

Oocyte Maturation ◽

Protective Role ◽

C Elegans ◽

Direct Target ◽

The One ◽

Actomyosin Cytoskeleton ◽

Embryonic Viability ◽

Anterior Posterior

Abstract Puromycin-sensitive aminopeptidases are found across phyla and are known to regulate the cell-cycle and play a protective role in neurodegenerative disease. PAM-1 is a puromycin-sensitive aminopeptidase important for meiotic exit and polarity establishment in the one-cell Caenorhabditis elegans embryo. Despite conservation of this aminopeptidase, little is known about its targets during development. In order to identify novel interactors, we conducted a suppressor screen and isolated four suppressing mutations in three genes that partially rescued the maternal-effect lethality of pam-1 mutants. Suppressed strains show improved embryonic viability and polarization of the anterior-posterior axis. We identified a missense mutation in wee-1.3 in one of these suppressed strains. WEE-1.3 is an inhibitory kinase that regulates maturation promoting factor. While the missense mutation suppressed polarity phenotypes in pam-1, it does so without restoring centrosome-cortical contact or altering the cortical actomyosin cytoskeleton. To see if PAM-1 and WEE-1.3 interact in other processes, we examined oocyte maturation. While depletion of wee-1.3 causes sterility due to precocious oocyte maturation, this effect was lessened in pam-1 worms, suggesting that PAM-1 and WEE-1.3 interact in this process. Levels of WEE-1.3 were comparable between wild-type and pam-1 strains, suggesting that WEE-1.3 is not a direct target of the aminopeptidase. Thus, we have established an interaction between PAM-1 and WEE-1.3 in multiple developmental processes and have identified suppressors that are likely to further our understanding of the role of puromycin-sensitive aminopeptidases during development.

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The Role of Tanycytes in the Hypothalamus-Pituitary-Thyroid Axis and the Possibilities for Their Genetic Manipulation

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-1065-1855 ◽

2019 ◽

Vol 128 (06/07) ◽

pp. 388-394

Author(s):

Helge Müller-Fielitz ◽

Markus Schwaninger

Keyword(s):

Energy Homeostasis ◽

Genetic Manipulation ◽

Heart Function ◽

Feedback Regulation ◽

Target Organs ◽

Pituitary Thyroid Axis ◽

Thyroid Axis ◽

Hpt Axis ◽

The Brain

AbstractThyroid hormone (TH) regulation is important for development, energy homeostasis, heart function, and bone formation. To control the effects of TH in target organs, the hypothalamus-pituitary-thyroid (HPT) axis and the tissue-specific availability of TH are highly regulated by negative feedback. To exert a central feedback, TH must enter the brain via specific transport mechanisms and cross the blood-brain barrier. Here, tanycytes, which are located in the ventral walls of the 3rd ventricle in the mediobasal hypothalamus (MBH), function as gatekeepers. Tanycytes are able to transport, sense, and modify the release of hormones of the HPT axis and are involved in feedback regulation. In this review, we focus on the relevance of tanycytes in thyrotropin-releasing hormone (TRH) release and review available genetic tools to investigate the physiological functions of these cells.

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Re-evaluating the role of ELT-3 in a GATA transcription factor circuit proposed to guide aging in C. elegans

Mechanisms of Ageing and Development ◽

10.1016/j.mad.2011.09.006 ◽

2012 ◽

Vol 133 (1) ◽

pp. 50-53 ◽

Cited By ~ 15

Author(s):

Tabitha Tonsaker ◽

Ryan M. Pratt ◽

James D. McGhee

Keyword(s):

Transcription Factor ◽

C Elegans ◽

Gata Transcription Factor

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The melanocortin system

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00434.2002 ◽

2003 ◽

Vol 284 (3) ◽

pp. E468-E474 ◽

Cited By ~ 264

Author(s):

Ira Gantz ◽

Tung M. Fong

Keyword(s):

Sexual Function ◽

Energy Homeostasis ◽

Melanocortin Receptors ◽

Experimental Basis ◽

Melanocortin System ◽

Genetic Studies ◽

Melanocortin Peptides ◽

Selective Agonists ◽

Made In

The melanocortin system consists of melanocortin peptides derived from the proopiomelanocortin gene, five melanocortin receptors, two endogenous antagonists, and two ancillary proteins. This review provides an abbreviated account of the basic biochemistry, pharmacology, and physiology of the melanocortin system and highlights progress made in four areas. In particular, recent pharmacological and genetic studies have affirmed the role of melanocortins in pigmentation, inflammation, energy homeostasis, and sexual function. Development of selective agonists and antagonists is expected to further facilitate the investigation of these complex physiological functions and provide an experimental basis for new pharmacotherapies.

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L-Carnitine in Drosophila: A Review

Antioxidants ◽

10.3390/antiox9121310 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1310

Author(s):

Maria Rosaria Carillo ◽

Carla Bertapelle ◽

Filippo Scialò ◽

Mario Siervo ◽

Gianrico Spagnuolo ◽

...

Keyword(s):

Transport System ◽

Essential Role ◽

Energy Homeostasis ◽

Current Knowledge ◽

Fatty Acyl ◽

Amino Acid Derivative ◽

Carnitine Transport ◽

Human Transport ◽

Drosophila Models

L-Carnitine is an amino acid derivative that plays a key role in the metabolism of fatty acids, including the shuttling of long-chain fatty acyl CoA to fuel mitochondrial β-oxidation. In addition, L-carnitine reduces oxidative damage and plays an essential role in the maintenance of cellular energy homeostasis. L-carnitine also plays an essential role in the control of cerebral functions, and the aberrant regulation of genes involved in carnitine biosynthesis and mitochondrial carnitine transport in Drosophila models has been linked to neurodegeneration. Drosophila models of neurodegenerative diseases provide a powerful platform to both unravel the molecular pathways that contribute to neurodegeneration and identify potential therapeutic targets. Drosophila can biosynthesize L-carnitine, and its carnitine transport system is similar to the human transport system; moreover, evidence from a defective Drosophila mutant for one of the carnitine shuttle genes supports the hypothesis of the occurrence of β-oxidation in glial cells. Hence, Drosophila models could advance the understanding of the links between L-carnitine and the development of neurodegenerative disorders. This review summarizes the current knowledge on L-carnitine in Drosophila and discusses the role of the L-carnitine pathway in fly models of neurodegeneration.

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Potential role of protein stabilizers in amelioration of Parkinson's disease and associated effects in transgenic Caenorhabditis elegans model expressing alpha-synuclein

RSC Advances ◽

10.1039/c5ra13546j ◽

2015 ◽

Vol 5 (95) ◽

pp. 77706-77715 ◽

Cited By ~ 4

Author(s):

Supinder Kaur ◽

Aamir Nazir

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

Caenorhabditis Elegans ◽

Potential Role ◽

Alpha Synuclein ◽

C Elegans

Studies employing transgenicC. elegansmodel show that trehalose, a protein stabilizer, alleviates manifestations associated with Parkinson's diseaseviaits inherent activity and through induction of autophagic machinery.

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