PMID- 34309811
OWN - NLM
STAT- MEDLINE
DCOM- 20211207
LR  - 20220531
IS  - 1995-8218 (Electronic)
IS  - 1673-7067 (Print)
IS  - 1995-8218 (Linking)
VI  - 37
IP  - 12
DP  - 2021 Dec
TI  - ubtor Mutation Causes Motor Hyperactivity by Activating mTOR Signaling in 
      Zebrafish.
PG  - 1658-1670
LID - 10.1007/s12264-021-00755-z [doi]
AB  - Mechanistic target of rapamycin (mTOR) signaling governs important physiological 
      and pathological processes key to cellular life. Loss of mTOR negative regulators 
      and subsequent over-activation of mTOR signaling are major causes underlying 
      epileptic encephalopathy. Our previous studies showed that UBTOR/KIAA1024/MINAR1 
      acts as a negative regulator of mTOR signaling, but whether UBTOR plays a role in 
      neurological diseases remains largely unknown. We therefore examined a zebrafish 
      model and found that ubtor disruption caused increased spontaneous embryonic 
      movement and neuronal activity in spinal interneurons, as well as the expected 
      hyperactivation of mTOR signaling in early zebrafish embryos. In addition, mutant 
      ubtor larvae showed increased sensitivity to the convulsant pentylenetetrazol, 
      and both the motor activity and the neuronal activity were up-regulated. These 
      phenotypic abnormalities in zebrafish embryos and larvae were rescued by 
      treatment with the mTORC1 inhibitor rapamycin. Taken together, our findings show 
      that ubtor regulates motor hyperactivity and epilepsy-like behaviors by elevating 
      neuronal activity and activating mTOR signaling.
CI  - (c) 2021. The Author(s).
FAU - Wang, Tiantian
AU  - Wang T
AD  - State Key Laboratory of Medical Neurobiology, Ministry of Education Frontiers 
      Center for Brain Science, and Institutes of Brain Science, Fudan University, 
      Shanghai, 200032, China.
FAU - Zhou, Mingshan
AU  - Zhou M
AD  - State Key Laboratory of Medical Neurobiology, Ministry of Education Frontiers 
      Center for Brain Science, and Institutes of Brain Science, Fudan University, 
      Shanghai, 200032, China.
FAU - Zhang, Quan
AU  - Zhang Q
AD  - State Key Laboratory of Medical Neurobiology, Ministry of Education Frontiers 
      Center for Brain Science, and Institutes of Brain Science, Fudan University, 
      Shanghai, 200032, China.
FAU - Zhang, Cuizhen
AU  - Zhang C
AD  - State Key Laboratory of Medical Neurobiology, Ministry of Education Frontiers 
      Center for Brain Science, and Institutes of Brain Science, Fudan University, 
      Shanghai, 200032, China.
FAU - Peng, Gang
AU  - Peng G
AD  - State Key Laboratory of Medical Neurobiology, Ministry of Education Frontiers 
      Center for Brain Science, and Institutes of Brain Science, Fudan University, 
      Shanghai, 200032, China. gangpeng@fudan.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20210726
PL  - Singapore
TA  - Neurosci Bull
JT  - Neuroscience bulletin
JID - 101256850
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Animals
MH  - *Hyperkinesis/genetics
MH  - Mutation/genetics
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
MH  - *Zebrafish/metabolism
PMC - PMC8643380
OTO - NOTNLM
OT  - Epilepsy
OT  - Hyperactivity
OT  - Ubtor
OT  - Zebrafish
OT  - mTOR
COIS- The authors claim that there are no conflicts of interest.
EDAT- 2021/07/27 06:00
MHDA- 2021/12/15 06:00
PMCR- 2021/07/26
CRDT- 2021/07/26 12:33
PHST- 2020/12/31 00:00 [received]
PHST- 2021/04/08 00:00 [accepted]
PHST- 2021/07/27 06:00 [pubmed]
PHST- 2021/12/15 06:00 [medline]
PHST- 2021/07/26 12:33 [entrez]
PHST- 2021/07/26 00:00 [pmc-release]
AID - 10.1007/s12264-021-00755-z [pii]
AID - 755 [pii]
AID - 10.1007/s12264-021-00755-z [doi]
PST - ppublish
SO  - Neurosci Bull. 2021 Dec;37(12):1658-1670. doi: 10.1007/s12264-021-00755-z. Epub 
      2021 Jul 26.