UBR-1 enzyme network regulates glutamate homeostasis to affect organismal behavior and developmental viability.

ABSTRACT: Johanson-Blizzard Syndrome (JBS) is an autosomal recessive spectrum disorder associated with the UBR-1 ubiquitin ligase that features developmental delay including motor abnormalities. Here, we demonstrate that C. elegans UBR-1 regulates high-intensity locomotor behavior and developmental viability via both ubiquitin ligase and scaffolding mechanisms. Super-resolution imaging with CRISPR-engineered UBR-1 and genetic results demonstrated that UBR-1 is expressed and functions in the nervous system including in pre-motor interneurons. To decipher mechanisms of UBR-1 function, we deployed CRISPR-based proteomics using C. elegans which identified a cadre of glutamate metabolic enzymes physically associated with UBR-1 including GLN-3, GOT-2.2, GFAT-1 and GDH-1. Similar to UBR-1, al

SUBMITTER: Pak JS 

PROVIDER: S-EPMC12324394 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature