AUTHOR=Mallick Avijit , Xu Leo , Mehta Sakshi , Taylor Shane K. B. , Hosein Hannah , Gupta Bhagwati P. 

TITLE=The FGFR4 Homolog KIN-9 Regulates Lifespan and Stress Responses in Caenorhabditis elegans

JOURNAL=Frontiers in Aging

VOLUME=3

YEAR=2022

URL=https://www.frontiersin.org/journals/aging/articles/10.3389/fragi.2022.866861

DOI=10.3389/fragi.2022.866861

ISSN=2673-6217

ABSTRACT=<p>Fibroblast growth factor receptors (FGFRs) regulate diverse biological processes in eukaryotes. The nematode <italic>Caenorhabditis elegans</italic> is a good animal model for studying the roles of FGFR signaling and its mechanism of regulation. In this study, we report that KIN-9 is an FGFR homolog in <italic>C. elegans</italic> that plays essential roles in aging and stress response maintenance. <italic>kin-9</italic> was discovered as a target of <italic>miR-246</italic>, a microRNA that is positively regulated by the Axin family member <italic>pry-1</italic>. We found that animals lacking <italic>kin-9</italic> function were long-lived and resistant to chemically induced stress. Furthermore, they showed a reduced expression of endoplasmic reticulum unfolded protein response (ER-UPR) pathway genes, suggesting that <italic>kin-9</italic> is required to maintain a normal ER-UPR. The analysis of GFP reporter-based expression in transgenic animals revealed that KIN-9 is localized in the intestine. Overall, our findings demonstrate that <italic>kin-9</italic> is regulated by <italic>miR-246</italic> and may function downstream of <italic>pry-1</italic>. This study prompts future investigations to understand the mechanism of miRNA-mediated FGFR function in maintaining aging and stress response processes.</p>