BMP signaling to pharyngeal muscle in the <i>C. elegans</i> response to a bacterial pathogen regulates anti-microbial peptide expression and pharyngeal pumping

Ciccarelli, Emma Jo; Bendelstein, Moshe; Yamamoto, Katerina K.; Reich, Hannah; Savage-Dunn, Cathy

doi:10.1091/mbc.e23-05-0185

Cited by 4 publications

(14 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The BMP-like Ligands DBL-1 and TIG-2 are Independently Required for C. elegans Survival on Bacterial Pathogen C. elegans has five TGF-β like ligands: DBL-1, DAF-7, UNC-129, TIG-2, and TIG-3. It is established that loss of DBL-1, one of two BMP-like ligands in C. elegans, reduces animal survival on bacterial pathogen [35][36]. In a variety of physiological contexts, heterodimers of BMP ligands are functionally required or outperform homodimers [39][40][41][42].…”

Section: Resultsmentioning

confidence: 99%

TGF-β ligand cross-subfamily interactions in the response of Caenorhabditis elegans to a bacterial pathogen

Ciccarelli,

Wing,

Bendelstein

et al. 2024

PLoS Genet

View full text Add to dashboard Cite

The Transforming Growth Factor beta (TGF-β) family consists of numerous secreted peptide growth factors that play significant roles in cell function, tissue patterning, and organismal homeostasis, including wound repair and immunity. Typically studied as homodimers, these ligands have the potential to diversify their functions through ligand interactions that may enhance, repress, or generate novel functions. In the nematode Caenorhabditis elegans, there are only five TGF-β ligands, providing an opportunity to dissect ligand interactions in fewer combinations than in vertebrates. As in vertebrates, these ligands can be divided into bone morphogenetic protein (BMP) and TGF-β/Activin subfamilies that predominantly signal through discrete signaling pathways. The BMP subfamily ligand DBL-1 has been well studied for its role in the innate immune response in C. elegans. Here we show that all five TGF-β ligands play a role in survival on bacterial pathogens. We also demonstrate that multiple TGF-β ligand pairs act nonredundantly as part of this response. We show that the two BMP-like ligands–DBL-1 and TIG-2–function independently of each other in the immune response, while TIG-2/BMP and the TGF-β/Activin-like ligand TIG-3 function together. Structural modeling supports the potential for TIG-2 and TIG-3 to form heterodimers. Additionally, we identify TIG-2 and TIG-3 as members of a rare subset of TGF-β ligands lacking the conserved cysteine responsible for disulfide linking mature dimers. Finally, we show that canonical DBL-1/BMP receptor and Smad signal transducers function in the response to bacterial pathogens, while components of the DAF-7 TGF-β/Activin signaling pathway do not play a major role in survival. These results demonstrate a novel potential for BMP and TGF-β/Activin subfamily ligands to interact and may provide a mechanism for distinguishing the developmental and homeostatic functions of these ligands from an acute response such as the innate immune response to bacterial pathogens.

show abstract

Section: Resultsmentioning

confidence: 99%

TGF-β ligand cross-subfamily interactions in the response of Caenorhabditis elegans to a bacterial pathogen

Ciccarelli,

Wing,

Bendelstein

et al. 2024

PLoS Genet

View full text Add to dashboard Cite

show abstract

“…Previous work from our lab and others has demonstrated that the BMP homolog DBL-1 functions in the innate immune response of C. elegans to pathogenic bacteria and fungi by inducing the expression of antimicrobial peptide genes in response to pathogen exposure [35][36][37][38]. Here we demonstrate that the DBL-1 ligand is only one of four TGF-β family ligands with a significant role in the immune response to two gram-negative bacterial pathogens.…”

Section: Introductionmentioning

confidence: 50%

Section: Resultsmentioning

confidence: 99%

“…Furthermore, tig-2 and tig-3 expression overlaps in neurons located adjacent to the pharynx, such as AFD and M2. We have shown that SMA-3/Smad is required in pharyngeal muscle for survival on bacterial pathogens [35], so TIG-2 and TIG-3 are produced in a location appropriate for signaling to SMA-3/Smad in the pharynx.…”

Section: Discussionmentioning

confidence: 98%

“…In contrast, TGF-β/Activin pathway components have minimal effects. We previously provided evidence that DBL-1 acts through SMA-3 to regulate antimicrobial peptide genes abf-2 and cnc-2 [35]. The survival deficit of sma-3 mutants, however, is more similar to that of tig-2 and tig-3 mutants.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Untitled

View full text Add to dashboard Cite

Genome-wide analysis of Smad and Schnurri transcription factors inC. elegansdemonstrates widespread interaction and a function in collagen secretion

Vora,

Dietz,

Wing

et al. 2024

Preprint

View full text Add to dashboard Cite

Smads and their transcription factor partners mediate the transcriptional responses of target cells to secreted ligands of the Transforming Growth Factor-β (TGF-β) family, including those of the conserved bone morphogenetic protein (BMP) family, yet only a small number of direct target genes have been well characterized. InC. elegans,the BMP2/4 ortholog DBL-1 regulates multiple biological functions, including body size, via a canonical receptor-Smad signaling cascade. Here, we identify functional binding sites for SMA-3/Smad and its transcriptional partner SMA-9/Schnurri based on ChIP-seq peaks (identified by modEncode) and expression differences of nearby genes identified from RNA-seq analysis of corresponding mutants. We found that SMA-3 and SMA-9 have both overlapping and unique target genes. At a genome-wide scale, SMA-3/Smad acts as a transcriptional activator, whereas SMA-9/Schnurri direct targets include both activated and repressed genes. Mutations insma-9partially suppress the small body size phenotype ofsma-3,suggesting some level of antagonism between these factors and challenging the prevailing model for Schnurri function. A functional analysis of target genes revealed a novel role in body size for genes involved in one-carbon metabolism and in the endoplasmic reticulum (ER) secretory pathway, including the disulfide reductasedpy-11.Our findings indicate that Smads and SMA-9/Schnurri have previously unappreciated complex genetic and genomic regulatory interactions that in turn regulate the secretion of extracellular components like collagen into the cuticle to mediate body size regulation.

show abstract

BMP signaling to pharyngeal muscle in the C. elegans response to a bacterial pathogen regulates anti-microbial peptide expression and pharyngeal pumping

Cited by 4 publications

References 53 publications

TGF-β ligand cross-subfamily interactions in the response of Caenorhabditis elegans to a bacterial pathogen

TGF-β ligand cross-subfamily interactions in the response of Caenorhabditis elegans to a bacterial pathogen

Untitled

Genome-wide analysis of Smad and Schnurri transcription factors inC. elegansdemonstrates widespread interaction and a function in collagen secretion

Contact Info

Product

Resources

About