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.

The Histone Chaperone Network Is Highly Conserved in Physarum polycephalum

“…For UBN and CABIN1 in C. elegans , no orthologues were retrieved in UniProt or by BLASTp. CePICD-1 (pry-1 interacting CABIN1 domain containing) was found in the literature as an orthologue of CABIN1 [ 69 ]. We did not identify CePQN-80 based on UBN protein sequence homology, but it was added in the phylogenetic analysis based on a recent study [ 70 ].…”

Neurotrophic factor MANF regulates autophagy and lysosome function to promote proteostasis inC. elegans

“…The duration and concentration are mentioned in figure legends. Acute treatments of tunicamycin (50 ng/µL) and paraquat (200 mM) were carried out in liquid by exposing animals for 4 hrs as described earlier [73].…”

“…All lifespan assays were carried out at 20°C on NGM agar plates seeded with E. coli OP50 bacteria as previously described (Mallick et al 2022). All lifespan experiments were repeated in triplicates.…”

“…Animals were exposed to desired concentrations of drugs on culture plates (Taylor et al 2021). Acute treatments of tunicamycin and paraquat were carried out in liquid by exposing animals to 50ng/µL and 200mM concentrations, respectively, for 4hrs as described earlier (Mallick et al 2022). A different tunicamycin concentration of 5µg/mL was used for Fig 1A-C and F-G to measure manf-1 and hsp-4 transcripts.…”