Ubiquitin carboxy-terminal hydrolase L1 binds to and stabilizes monoubiquitin in neuron.
Mammalian neuronal cells abundantly express a deubiquitylating enzyme, ubiquitin carboxy-terminal hydrolase 1 (UCH L1). Mutations in UCH L1 are linked to Parkinson's disease as well as gracile axonal dystrophy (gad) in mice. In contrast to the UCH L3 isozyme that is universally expressed in all tissues, UCH L1 is expressed exclusively in neurons and testis/ovary. We found that UCH L1 associates and colocalizes with monoubiquitin and elongates ubiquitin half-life. The gad mouse, in which the function of UCH L1 is lost, exhibited a reduced level of monoubiquitin in neurons. In contrast, overexpression of UCH L1 caused an increase in the level of ubiquitin in both cultured cells and mice. These data suggest that UCH L1, with avidity and affinity for ubiquitin, insures ubiquitin stability within neurons. This study is the first to show the function of UCH L1 in vivo.
Osaka
Hitoshi
H
Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, 187-8502, Japan.
Wang
Yu-Lai
YL
Takada
Koji
K
Takizawa
Shuichi
S
Setsuie
Rieko
R
Li
Hang
H
Sato
Yae
Y
Nishikawa
Kaori
K
Sun
Ying-Jie
YJ
Sakurai
Mikako
M
Harada
Takayuki
T
Hara
Yoko
Y
Kimura
Ichiro
I
Chiba
Shigeru
S
Namikawa
Kazuhiko
K
Kiyama
Hiroshi
H
Noda
Mami
M
Aoki
Shunsuke
S
Wada
Keiji
K
D000818:Animals; D001921:Brain / Q000201:enzymology; D017353:Gene Deletion; D051379:Mice / Q000235:genetics; D008817:Mice, Mutant Strains; D009474:Neurons / Q000201:enzymology*; D014162:Transfection; D025801:Ubiquitin / Q000378:metabolism*; D043222:Ubiquitin Thiolesterase / Q000235:genetics / Q000378:metabolism*
D025801:Ubiquitin; D043222:Ubiquitin Thiolesterase