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Cabin1 domain-containing gene picd-1 interacts with pry-1/Axin to regulate multiple processes in Caenorhabditis elegans

ABSTRACT: The Axin family of scaffolding proteins control diverse processes, such as facilitating the interactions between cellular components and providing specificity to signaling pathways. While several Axin family members have been discovered in metazoans and shown to play crucial roles, their mechanism of action are not well understood. The Caenorhabditis elegans Axin homolog, pry-1, is a powerful tool for identifying interacting genes and downstream effectors that function in a conserved manner to regulate Axin-mediated signaling. Our lab and others have established pry-1’s essential role in developmental processes that affect the reproductive system, seam cells, and a posterior P lineage cell, P11.p. Additionally, pry-1 is crucial for lipid metabolism, stress responses, and aging. In this study, we expanded on our previous work on pry-1 by reporting a novel interacting gene named picd-1 (pry-1-interacting and Cabin1 domain-containing). PICD-1 protein shares sequence conservation with CABIN1, a component of the HUCA complex. Our findings have revealed that PICD-1 is involved in several pry-1-mediated processes, including stress response and lifespan maintenance. picd-1’s expression overlapped with that of pry-1 in multiple tissues throughout the lifespan. Furthermore, PRY-1 and PICD-1 inhibited CREB-regulated transcriptional coactivator homolog CRTC-1, which promotes longevity in a calcineurin-dependent manner. Overall, our study has demonstrated that picd-1 is necessary for mediating pry-1 function and provides the basis to investigate whether Cabin-1 domain-containing protein plays a similar role in Axin signaling in other systems.

SUBMITTER: Mallick A

PROVIDER: S-EPMC9283418 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundCaenorhabditis elegans seam cells serve as a good model to understand how genes and signaling pathways interact to control asymmetric cell fates. The stage-specific pattern of seam cell division is coordinated by a genetic network that includes WNT asymmetry pathway components WRM-1, LIT-1, and POP-1, as well as heterochronic microRNAs (miRNAs) and their downstream targets. Mutations in pry-1, a negative regulator of WNT signaling that belongs to the Axin family, were shown to cause seam cell defects; however, the mechanism of PRY-1 action and its interactions with miRNAs remain unclear.ResultsWe found that pry-1 mutants in C. elegans exhibit seam cell, cuticle, and alae defects. To examine this further, a miRNA transcriptome analysis was carried out, which showed that let-7 (miR-48, miR-84, miR-241) and lin-4 (lin-4, miR-237) family members were upregulated in the absence of pry-1 function. Similar phenotypes and patterns of miRNA overexpression were also observed in C. briggsae pry-1 mutants, a species that is closely related to C. elegans. RNA interference-mediated silencing of wrm-1 and lit-1 in the C. elegans pry-1 mutants rescued the seam cell defect, whereas pop-1 silencing enhanced the phenotype, suggesting that all three proteins are likely important for PRY-1 function in seam cells. We also found that these miRNAs were overexpressed in pop-1 hypomorphic animals, suggesting that PRY-1 may be required for POP-1-mediated miRNA suppression. Analysis of the let-7 and lin-4-family heterochronic targets, lin-28 and hbl-1, showed that both genes were significantly downregulated in pry-1 mutants, and furthermore, lin-28 silencing reduced the number of seam cells in mutant animals.ConclusionsOur results show that PRY-1 plays a conserved role to maintain normal expression of heterochronic miRNAs in nematodes. Furthermore, we demonstrated that PRY-1 acts upstream of the WNT asymmetry pathway components WRM-1, LIT-1, and POP-1, and miRNA target genes in seam cell development.

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Cabin1 domain-containing gene picd-1 interacts with pry-1/Axin to regulate multiple processes in Caenorhabditis elegans

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