The Derlin-1-Stat5b axis maintains homeostasis of adult hippocampal neurogenesis

Naoya Murao, Taito Matsuda, Hisae Kadowaki, Yosuke Matsushita, Kousuke Tanimoto, Toyomasa Katagiri, Kinichi Nakashima, Hideki Nishitoh

Research output: Contribution to journalArticlepeer-review

Abstract

Adult neural stem cells (NSCs) in the hippocampal dentate gyrus continuously proliferate and generate new neurons throughout life. Although various functions of organelles are closely related to the regulation of adult neurogenesis, the role of endoplasmic reticulum (ER)-related molecules in this process remains largely unexplored. Here we show that Derlin-1, an ER-associated degradation component, spatiotemporally maintains adult hippocampal neurogenesis through a mechanism distinct from its established role as an ER quality controller. Derlin-1 deficiency in the mouse central nervous system leads to the ectopic localization of newborn neurons and impairs NSC transition from active to quiescent states, resulting in early depletion of hippocampal NSCs. As a result, Derlin-1-deficient mice exhibit phenotypes of increased seizure susceptibility and cognitive dysfunction. Reduced Stat5b expression is responsible for adult neurogenesis defects in Derlin-1-deficient NSCs. Inhibition of histone deacetylase activity effectively induces Stat5b expression and restores abnormal adult neurogenesis, resulting in improved seizure susceptibility and cognitive dysfunction in Derlin-1-deficient mice. Our findings indicate that the Derlin-1-Stat5b axis is indispensable for the homeostasis of adult hippocampal neurogenesis.

Original languageEnglish
Pages (from-to)3678-3706
Number of pages29
JournalEMBO Reports
Volume25
Issue number8
DOIs
Publication statusPublished - Aug 9 2024
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Genetics

Fingerprint

Dive into the research topics of 'The Derlin-1-Stat5b axis maintains homeostasis of adult hippocampal neurogenesis'. Together they form a unique fingerprint.

Cite this