KF-1 Ubiquitin Ligase: An Anxiety Suppressor.
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.
Hashimoto-Gotoh
Tamotsu
T
Department of Biochemistry and Molecular Genetics, Research Institute for Neurological Diseases and Geriatrics, Kyoto Prefectural University of Medicine Japan.
Iwabe
Naoyuki
N
Tsujimura
Atsushi
A
Takao
Keizo
K
Miyakawa
Tsuyoshi
T