First Author | Hashimoto-Gotoh T | Year | 2009 |
Journal | Front Neurosci | Volume | 3 |
Issue | 1 | Pages | 15-24 |
PubMed ID | 19753093 | Mgi Jnum | J:154854 |
Mgi Id | MGI:4410322 | Doi | 10.3389/neuro.01.004.2009 |
Citation | Hashimoto-Gotoh T, et al. (2009) KF-1 Ubiquitin Ligase: An Anxiety Suppressor. Front Neurosci 3(1):15-24 |
abstractText | 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. |