RRC ID 76024
Author Otarigho B, Aballay A.
Title Immunity-longevity tradeoff neurally controlled by GABAergic transcription factor PITX1/UNC-30.
Journal Cell Rep
Abstract A body of evidence indicates that metazoan immune and aging pathways are largely interconnected, but the mechanisms involved in their homeostatic control remain unclear. In this study, we find that the PITX (paired-like homeodomain) transcription factor UNC-30 controls the tradeoff between immunity and longevity from the nervous system in Caenorhabditis elegans. PITX/UNC-30 functional loss enhances immunity in a GATA/ELT-2- and p38 MAPK/PMK-1-dependent manner and reduced longevity by activating MXD/MDL-1 and the C2H2-type zinc finger transcription factor PQM-1. The immune inhibitory and longevity stimulatory functions of PITX/UNC-30 require the sensory neuron ASG and a signaling pathway controlled by NPR-1, which is a G protein-coupled receptor related to mammalian neuropeptide Y receptors. Our findings uncover a suppressive role of GABAergic signaling in the neural control of a biological tradeoff where energy is allocated toward immunity at the expense of longevity.
Volume 35(8)
Pages 109187
Published 2021-5-25
DOI 10.1016/j.celrep.2021.109187
PII S2211-1247(21)00533-7
PMID 34038721
PMC PMC8227953
MeSH Animals Caenorhabditis elegans / metabolism* Caenorhabditis elegans Proteins / metabolism* Homeodomain Proteins / metabolism* Immunity, Innate / immunology* Longevity* Nuclear Proteins / metabolism* Pseudomonas aeruginosa / metabolism* Transcription Factors / metabolism
Resource
C.elegans tm311