KF-1 ubiquitin ligase: An anxiety suppressor

Tamotsu Hashimoto-Gotoh, Naoyuki Iwabe, Atsushi Tsujimura, Keizo Takao, Tsuyoshi Miyakawa

Research output: Contribution to journalReview article

7 Citations (Scopus)

Abstract

Anxiety is an instinct that may have developed to promote adaptive survival by evading unnecessary danger. However, excessive anxiety is disruptive and can be a basic disorder of other psychiatric diseases such as depression. The KF-1, a ubiquitin ligase located on the endoplasmic reticulum (ER), may prevent excessive anxiety; kf-1-/- mice exhibit selectively elevated anxiety-like behavior against light or heights. It is surmised that KF-1 degrades some target proteins, responsible for promoting anxiety, through the ER-associated degradation pathway, similar to Parkin in Parkinson's disease (PD). Parkin, another ER-ubiquitin ligase, prevents the degeneration of dopaminergic neurons by degrading the target proteins responsible for PD. Molecular phylogenetic studies have revealed that the prototype of kf-1 appeared in the very early phase of animal evolution but was lost, unlike parkin, in the lineage leading up to Drosophila. Therefore, kf-1-/- mice may be a powerful tool for elucidating the molecular mechanisms involved in emotional regulation, and for screening novel anxiolytic/antidepressant compounds.

Original languageEnglish
Article numberArticle 1
JournalFrontiers in Neuroscience
Volume3
Issue numberMAY
DOIs
Publication statusPublished - 01-12-2009

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)

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    Hashimoto-Gotoh, T., Iwabe, N., Tsujimura, A., Takao, K., & Miyakawa, T. (2009). KF-1 ubiquitin ligase: An anxiety suppressor. Frontiers in Neuroscience, 3(MAY), [Article 1]. https://doi.org/10.3389/neuro.01.004.2009