TY - JOUR
T1 - KF-1 ubiquitin ligase
T2 - An anxiety suppressor
AU - Hashimoto-Gotoh, Tamotsu
AU - Iwabe, Naoyuki
AU - Tsujimura, Atsushi
AU - Takao, Keizo
AU - Miyakawa, Tsuyoshi
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=79952088963&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79952088963&partnerID=8YFLogxK
U2 - 10.3389/neuro.01.004.2009
DO - 10.3389/neuro.01.004.2009
M3 - Review article
AN - SCOPUS:79952088963
SN - 1662-4548
VL - 3
JO - Frontiers in Neuroscience
JF - Frontiers in Neuroscience
IS - MAY
M1 - Article 1
ER -