scholarly journals The neogenin/DCC homolog UNC-40 promotes BMP signaling via the RGM protein DRAG-1 in C. elegans

Development ◽  
2013 ◽  
Vol 140 (19) ◽  
pp. 4070-4080 ◽  
Author(s):  
Chenxi Tian ◽  
Herong Shi ◽  
Shan Xiong ◽  
Fenghua Hu ◽  
Wen-Cheng Xiong ◽  
...  
Keyword(s):  
Bmp Signaling ◽  
C Elegans

scholarly journals A neuronal thermostat controls membrane fluidity in C. elegans

2019 ◽  
Author(s):  
L Chauve ◽  
S Murdoch ◽  
F. Masoudzadeh ◽  
F. Hodge ◽  
A. Lopez-Clavijo ◽  
...  
Keyword(s):  
Membrane Fluidity ◽  
Unsaturated Fatty Acids ◽  
Bmp Signaling ◽  
Peripheral Tissues ◽  
Over Expression ◽  
C Elegans ◽  
Shock Response ◽  
Lipid Desaturation ◽  
Neuronal Stress ◽  
Fluidity Of Membranes

SummaryAn organisms’ ability to adapt to heat can be key to its survival. Cells adapt to temperature shifts by adjusting lipid desaturation levels and the fluidity of membranes in a process that is thought to be controlled cell autonomously. We have discovered that subtle, step-wise increments in ambient temperature can lead to the conserved heat shock response being activated in head neurons of C. elegans. This response is exactly opposite to the expression of the lipid desaturase FAT-7 in the worm’s gut. We find that the over-expression of the master regulator of this response, Hsf-1, in head neurons, causes extensive fat remodeling to occur across tissues. These changes include a decrease in FAT-7 expression and a shift in the levels of unsaturated fatty acids in the plasma membrane. These shifts are in line with membrane fluidity requirements to survive in warmer temperatures. We have identified that the cGMP receptor, TAX-2/TAX-4, as well as TGF-β/BMP signaling, as key players in the transmission of neuronal stress to peripheral tissues. This is the first study to suggest that a thermostat-based mechanism can centrally coordinate membrane fluidity in response to warm temperatures across tissues in multicellular animals.

scholarly journals C. elegans DAF-16/FOXO interacts with TGF-ß/BMP signaling to induce germline tumor formation via mTORC1 activation

PLoS Genetics ◽  
2017 ◽  
Vol 13 (5) ◽  
pp. e1006801 ◽  
Author(s):  
Wenjing Qi ◽  
Yijian Yan ◽  
Dietmar Pfeifer ◽  
Erika Donner v. Gromoff ◽  
Yimin Wang ◽  
...  
Keyword(s):  
Tumor Formation ◽  
Bmp Signaling ◽  
C Elegans ◽  
Mtorc1 Activation

scholarly journals Mechanism of Interaction of BMP and Insulin Signaling in C. elegans Development and Homeostasis

2019 ◽  
Author(s):  
James F. Clark ◽  
Emma J. Ciccarelli ◽  
Gehan Ranepura ◽  
Muhammad S. Hasan ◽  
Alicia Meléndez ◽  
...  
Keyword(s):  
Bmp Signaling ◽  
Lipid Homeostasis ◽  
Signaling Crosstalk ◽  
C Elegans ◽  
Morphogenetic Protein ◽  
Autophagy Induction ◽  
Dauer Formation ◽  
And Function ◽  
Modes Of Interaction ◽  
Molecular Components

AbstractA small number of peptide growth factor ligands are used repeatedly in development and homeostasis to drive programs of cell differentiation and function. Cells and tissues must integrate inputs from these diverse signals correctly, while failure to do so leads to pathology, reduced fitness, or death. Previous work using the nematode C. elegans identified an interaction between the bone morphogenetic protein (BMP) and insulin/IGF-1-like signaling (IIS) pathways in the regulation of lipid homeostasis. The molecular components required for this interaction, however, were not known. Here we report that INS-4, one of 40 insulin-like peptides (ILPs), is specifically regulated by BMP signaling to modulate fat accumulation. Furthermore, we find that the IIS transcription factor DAF-16/FoxO, but not SKN-1/Nrf, acts downstream of BMP signaling in lipid homeostasis. Interestingly, BMP activity alters sensitivity of these two transcription factors to IIS-promoted cytoplasmic retention in opposite ways. Finally, we probe the extent of BMP and IIS interactions by testing two additional IIS functions, dauer formation and autophagy induction. Coupled with our previous work and that of other groups, we conclude that BMP and IIS pathways have at least three modes of interaction: independent, epistatic, and antagonistic. The molecular interactions we identify provide new insight into mechanisms of signaling crosstalk and potential therapeutic targets for IIS-related pathologies such as diabetes and metabolic syndrome.

scholarly journals The C. elegans SMOC-1 protein acts cell non-autonomously to promote bone morphogenetic protein signaling

2018 ◽  
Author(s):  
Melisa S. DeGroot ◽  
Herong Shi ◽  
Alice Eastman ◽  
Alexandra N. McKillop ◽  
Jun Liu
Keyword(s):  
Body Size ◽  
Bone Morphogenetic Protein ◽  
Calcium Binding ◽  
Binding Protein ◽  
Calcium Binding Protein ◽  
Bmp Signaling ◽  
C Elegans ◽  
Morphogenetic Protein ◽  
Positive Modulator ◽  
Bmp Pathway

ABSTRACTBone morphogenetic protein (BMP) signaling regulates many different developmental and homeostatic processes in metazoans. The BMP pathway is conserved in Caenorhabditis elegans, and is known to regulate body size and mesoderm development. We have identified the C. elegans smoc-1 (Secreted MOdular Calcium binding protein-1) gene as a new player in the BMP pathway. smoc-1(0) null mutants have a small body size, while overexpression of smoc-1 led to a long body size and increased expression of the RAD-SMAD BMP reporter, suggesting that SMOC-1 acts as a positive modulator of BMP signaling. Using double mutant analysis, we showed that SMOC-1 antagonizes the function of the glypican LON-2 and acts through the BMP ligand DBL-1 to regulate BMP signaling. Moreover, SMOC-1 appears to specifically regulate BMP signaling without significant involvement in a TGFβ-like pathway that regulates dauer development. We found that smoc-1 is expressed in multiple tissues, including cells of the pharynx, intestine, and posterior hypodermis, and that the expression of smoc-1 in the intestine is positively regulated by BMP signaling. We further established that SMOC-1 functions cell non-autonomously to regulate body size. Human SMOC1 and SMOC2 can each partially rescue the smoc-1(0) mutant phenotype, suggesting that SMOC-1’s function in modulating BMP signaling is evolutionarily conserved. Together, our findings highlight a conserved role of SMOC proteins in modulating BMP signaling in metazoans.ARTICLE SUMMARYBMP signaling is critical for development and homeostasis in metazoans, and is under tight regulation. We report the identification and characterization of a Secreted MOdular Calcium binding protein SMOC-1 as a positive modulator of BMP signaling in C. elegans. We established that SMOC-1 antagonizes the function of LON-2/glypican and acts through the DBL-1/BMP ligand to promote BMP signaling. We identified smoc-1-expressing cells, and demonstrated that SMOC-1 acts cell non-autonomously and in a positive feedback loop to regulate BMP signaling. We also provide evidence suggesting that the function of SMOC proteins in the BMP pathway is conserved from worms to humans.

scholarly journals C. elegans DBL-1/BMP Regulates Lipid Accumulation via Interaction with Insulin Signaling

2017 ◽  
Author(s):  
JF Clark ◽  
M Meade ◽  
G Ranepura ◽  
DH Hall ◽  
C Savage-Dunn
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplet ◽  
Lipid Accumulation ◽  
Metabolic Disorders ◽  
Bmp Signaling ◽  
Lipid Homeostasis ◽  
Metabolic Homeostasis ◽  
C Elegans ◽  
Lipid Droplet Size ◽  
Lipid Stores

AbstractMetabolic homeostasis is coordinately controlled by diverse inputs, which must be understood to combat metabolic disorders. Here we introduce DBL-1, the C. elegans BMP2/4 homolog, as a significant regulator of lipid homeostasis. We used neutral lipid staining and a lipid droplet marker to demonstrate that both increases and decreases in DBL-1/BMP signaling result in reduced lipid stores and lipid droplet count. We find that lipid droplet size, however, correlates positively with the level of DBL 1/BMP signaling. Regulation of lipid accumulation in the intestine occurs through non-cell-autonomous signaling, since expression of SMA-3, a Smad signal transducer, in the epidermis (hypodermis) is sufficient to rescue the loss of lipid accumulation. Finally, genetic evidence indicates that DBL-1/BMP functions upstream of Insulin/IGF-1 Signaling (IIS) in lipid metabolism. We conclude that BMP signaling regulates lipid metabolism in C. elegans through inter-organ signaling to IIS, shedding light on a less well-studied regulatory mechanism for metabolic homeostasis.

scholarly journals The C. elegans TspanC8 tetraspanin TSP-14 exhibits isoform-specific localization and function

2021 ◽  
Author(s):  
Zhiyu Liu ◽  
Herong Shi ◽  
Jun Liu
Keyword(s):  
Amino Acids ◽  
Expression Patterns ◽  
Basolateral Membrane ◽  
Living Organism ◽  
Distribution Patterns ◽  
Biochemical Properties ◽  
Bmp Signaling ◽  
Mesoderm Development ◽  
C Elegans

Tetraspanin proteins are a unique family of highly conserved four-pass transmembrane proteins in metazoans. While much is known about their biochemical properties, the in vivo functions and distribution patterns of different tetraspanin proteins are less understood. Previous studies have shown that two paralogous tetraspanins that belong to the TspanC8 subfamily, TSP12 and TSP-14, function redundantly to promote both Notch signaling and bon morphogenetic protein (BMP) signaling in C. elegans. TSP-14 has two isoforms, TSP-14A and TSP-14B, where TSP-14B has an additional 24 amino acids at its N-terminus compared to TSP-14A. By generating isoform specific knock-ins and knock-outs using CRISPR, we found that TSP-14A and TSP-14B share distinct as well as overlapping expression patterns and functions. While TSP14A functions redundantly with TSP-12 to regulate body size and embryonic and vulva development, TSP-14B primarily functions redundantly with TSP-12 to regulate postembryonic mesoderm development. Importantly, TSP-14A and TSP-14B exhibit distinct subcellular localization patterns. TSP-14A is localized apically and on early and late endosomes. TSP-14B is localized to the basolateral cell membrane. We further identified a di-leucine motif within the Nterminal 24 amino acids of TSP-14B that serves as a basolateral membrane targeting sequence, and showed that the basolateral membrane localization of TSP-14B is important for its function. Our work highlights the diverse and intricate functions of TspanC8 tetraspanins in C. elegans, and demonstrates the importance of dissecting the functions of these important proteins in an intact living organism.

The Drosophila gene Medea demonstrates the requirement for different classes of Smads in dpp signaling

Development ◽  
1998 ◽  
Vol 125 (8) ◽  
pp. 1519-1528 ◽  
Author(s):  
P. Das ◽  
L.L. Maduzia ◽  
H. Wang ◽  
A.L. Finelli ◽  
S.H. Cho ◽  
...  
Keyword(s):  
Transforming Growth Factor Beta ◽  
Transforming Growth Factor ◽  
Human Tumor ◽  
Suppressor Gene ◽  
Bmp Signaling ◽  
Class I ◽  
Tgf Beta ◽  
C Elegans ◽  
Sequence Similarities ◽  
Close Homolog

Signals from transforming growth factor-beta (TGF-beta) ligands are transmitted within the cell by members of the Smad family, which can be grouped into three classes based on sequence similarities. Our previous identification of both class I and II Smads functioning in a single pathway in C. elegans, raised the issue of whether the requirement for Smads derived from different classes is a general feature of TGF-beta signaling. We report here the identification of a new Drosophila class II Smad, Medea, a close homolog of the human tumor-suppressor gene DPC4. Embryos from germline clones of both Medea and Mad (a class I Smad) are ventralized, as are embryos null for the TGF-beta-like ligand decapentaplegic (dpp). Loss of Medea also blocks dpp signaling during later development, suggesting that Medea, like Mad, is universally required for dpp signaling. Furthermore, we show that the necessity for these two closely related, non-redundant Smads, is due to their different signaling properties - upon activation of the Dpp pathway, Mad is required to actively translocate Medea into the nucleus. These results provide a paradigm for, and distinguish between, the requirement for class I and II Smads in Dpp/BMP signaling.

scholarly journals Feedback regulation of BMP signaling by C. elegans cuticle collagens

2019 ◽  
Author(s):  
Uday Madaan ◽  
Lionel Faure ◽  
Albar Chowdhury ◽  
Shahrear Ahmed ◽  
Emma J. Ciccarelli ◽  
...  
Keyword(s):  
Body Size ◽  
Regulation Of Gene Expression ◽  
Feedback Regulation ◽  
Bmp Signaling ◽  
Physical Separation ◽  
C Elegans ◽  
Morphogenetic Protein ◽  
Cellular Responsiveness ◽  
Collagen Genes ◽  
Cuticle Collagens

AbstractCellular responsiveness to environmental cues, including changes in extracellular matrix (ECM), is critical for normal processes such as development and wound healing, but can go awry, as in oncogenesis and fibrosis. One type of molecular pathway allowing this responsiveness is the bone morphogenetic protein (BMP) signaling pathway. Due to their broad and potent functions, BMPs and their signaling pathways are highly regulated at multiple levels. In Caenorhabditis elegans, the BMP ligand DBL-1 is a major regulator of body size. We have previously shown that DBL-1/BMP signaling determines body size through transcriptional regulation of cuticle collagen genes. We have now obtained evidence of feedback regulation of DBL-1/BMP by collagen genes. We analyzed four DBL-1-regulated collagen genes that affect body size. Here we show that inactivation of any one of these cuticle collagen genes reduces DBL-1/BMP signaling, as measured by a Smad activity reporter. Furthermore, we find that depletion of these collagens reduces GFP::DBL-1 fluorescence, and acts unexpectedly at the level of dbl-1 transcription. We therefore conclude that cuticle, a type of ECM, impinges on DBL-1/BMP expression and signaling. In contrast to other characterized examples, however, the feedback regulation of DBL-1/BMP signaling by collagens is likely to be contact-independent, due to the physical separation of the cuticle from DBL-1-expressing cells in the ventral nerve cord. Our results provide an entry point into a novel mechanism of regulation of BMP signaling, with broader implications for mechanical regulation of gene expression in general.

The glycomes of Caenorhabditis elegans and other model organisms

2002 ◽  
Vol 69 ◽  
pp. 117-134 ◽  
Author(s):  
Stuart M. Haslam ◽  
David Gems ◽  
Howard R. Morris ◽  
Anne Dell
Keyword(s):  
Caenorhabditis Elegans ◽  
Current Knowledge ◽  
Structural Data ◽  
Model Organisms ◽  
Entire Genome ◽  
C Elegans ◽  
The Face ◽  
Area Of Concern ◽  
Nematode Worm

There is no doubt that the immense amount of information that is being generated by the initial sequencing and secondary interrogation of various genomes will change the face of glycobiological research. However, a major area of concern is that detailed structural knowledge of the ultimate products of genes that are identified as being involved in glycoconjugate biosynthesis is still limited. This is illustrated clearly by the nematode worm Caenorhabditis elegans, which was the first multicellular organism to have its entire genome sequenced. To date, only limited structural data on the glycosylated molecules of this organism have been reported. Our laboratory is addressing this problem by performing detailed MS structural characterization of the N-linked glycans of C. elegans; high-mannose structures dominate, with only minor amounts of complex-type structures. Novel, highly fucosylated truncated structures are also present which are difucosylated on the proximal N-acetylglucosamine of the chitobiose core as well as containing unusual Fucα1–2Gal1–2Man as peripheral structures. The implications of these results in terms of the identification of ligands for genomically predicted lectins and potential glycosyltransferases are discussed in this chapter. Current knowledge on the glycomes of other model organisms such as Dictyostelium discoideum, Saccharomyces cerevisiae and Drosophila melanogaster is also discussed briefly.

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