Comprehensive identification of ubiquitin-like 3 (UBL3)-interacting proteins in the mouse brain

Hiroshi Ageta, Tomoki Nishioka, Hisateru Yamaguchi, Kunihiro Tsuchida, Natsumi Ageta-Ishihara

Research output: Contribution to journalArticlepeer-review

Abstract

Discovery of novel post-translational modifications provides new insights into changes in protein function, localization, and stability. They are also key elements in understanding disease mechanisms and developing therapeutic strategies. We have previously reported that ubiquitin-like 3 (UBL3) serves as a novel post-translational modifier that is highly expressed in the cerebral cortex and hippocampus, in addition to various other organs, and that 60% of proteins contained in small extracellular vesicles (sEVs), including exosomes, are influenced by UBL3. In this study, we generated transgenic mice expressing biotinylated UBL3 in the forebrain under control of the alpha-CaMKII promoter (Ubl3Tg/+). Western blot analysis revealed that the expression of UBL3 in the cerebral cortex and hippocampus was 6- to 7-fold higher than that in the cerebellum. Therefore, we performed immunoprecipitation of protein extracts from the cerebral cortex of Ubl3+/+ and Ubl3Tg/+ mice using avidin beads to comprehensively discover UBL3 interacting proteins, identifying 35 new UBL3 interacting proteins. Nine proteins were annotated as extracellular exosomes. Gene Ontology (GO) analysis suggested a new relationship between sEVs and RNA metabolism in neurodegenerative diseases. We confirmed the association of endogenous UBL3 with the RNA-binding proteins FUS and HPRT1—both listed in the Neurodegenerative Diseases Variation Database (NDDVD)—and with LYPLA1, which is involved in Huntington’s disease, using immunoprecipitation (IP)-western blotting analysis. These UBL3 interacting proteins will accelerate the continued elucidation of sEV research about proteins regulated by novel post-translational modifications by UBL3 in the brain.

Original languageEnglish
Article number57
JournalMolecular brain
Volume17
Issue number1
DOIs
Publication statusPublished - 12-2024

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cellular and Molecular Neuroscience

Fingerprint

Dive into the research topics of 'Comprehensive identification of ubiquitin-like 3 (UBL3)-interacting proteins in the mouse brain'. Together they form a unique fingerprint.

Cite this