PMID- 30021166
OWN - NLM
STAT- MEDLINE
DCOM- 20191203
LR  - 20200306
IS  - 2211-1247 (Electronic)
VI  - 24
IP  - 3
DP  - 2018 Jul 17
TI  - Neuron-Specific Menin Deletion Leads to Synaptic Dysfunction and Cognitive 
      Impairment by Modulating p35 Expression.
PG  - 701-712
LID - S2211-1247(18)30965-3 [pii]
LID - 10.1016/j.celrep.2018.06.055 [doi]
AB  - Menin (MEN1) is a critical modulator of tissue development and maintenance. As 
      such, MEN1 mutations are associated with multiple endocrine neoplasia type 1 
      (MEN1) syndrome. Although menin is abundantly expressed in the nervous system, 
      little is known with regard to its function in the adult brain. Here, we 
      demonstrate that neuron-specific deletion of Men1 (CcKO) affects dendritic 
      branching and spine formation, resulting in defects in synaptic function, 
      learning, and memory. Furthermore, we find that menin binds to the p35 promoter 
      region to facilitate p35 transcription. As a primary Cdk5 activator, p35 is 
      expressed mainly in neurons and is critical for brain development and synaptic 
      plasticity. Restoration of p35 expression in the hippocampus and cortex of Men1 
      CcKO mice rescues synaptic and cognitive deficits associated with Men1 deletion. 
      These results reveal a critical role for menin in synaptic and cognitive function 
      by modulating the p35-Cdk5 pathway.
CI  - Copyright (c) 2018 The Author(s). Published by Elsevier Inc. All rights reserved.
FAU - Zhuang, Kai
AU  - Zhuang K
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China.
FAU - Huang, Changquan
AU  - Huang C
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China.
FAU - Leng, Lige
AU  - Leng L
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China.
FAU - Zheng, Honghua
AU  - Zheng H
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China.
FAU - Gao, Yuehong
AU  - Gao Y
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China.
FAU - Chen, Guimiao
AU  - Chen G
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China.
FAU - Ji, Zhilin
AU  - Ji Z
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China.
FAU - Sun, Hao
AU  - Sun H
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China.
FAU - Hu, Yu
AU  - Hu Y
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China.
FAU - Wu, Di
AU  - Wu D
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China.
FAU - Shi, Meng
AU  - Shi M
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China.
FAU - Li, Huifang
AU  - Li H
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China.
FAU - Zhao, Yingjun
AU  - Zhao Y
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China; Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery 
      Institute, La Jolla, CA 92037, USA.
FAU - Zhang, Yunwu
AU  - Zhang Y
AD  - Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La 
      Jolla, CA 92037, USA.
FAU - Xue, Maoqiang
AU  - Xue M
AD  - Department of Basic Medical Science, Medical College, Xiamen University, Xiamen, 
      Fujian 361102, China.
FAU - Bu, Guojun
AU  - Bu G
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China; Department of Neuroscience, Mayo Clinic, Jacksonville, FL 32224, 
      USA.
FAU - Huang, Timothy Y
AU  - Huang TY
AD  - Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery Institute, La 
      Jolla, CA 92037, USA.
FAU - Xu, Huaxi
AU  - Xu H
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China; Neuroscience Initiative, Sanford Burnham Prebys Medical Discovery 
      Institute, La Jolla, CA 92037, USA.
FAU - Zhang, Jie
AU  - Zhang J
AD  - Fujian Provincial Key Laboratory of Neurodegenerative Disease and Aging Research, 
      Institute of Neuroscience, Medical College, Xiamen University, Xiamen, Fujian 
      361102, China. Electronic address: jiezhang@xmu.edu.cn.
LA  - eng
GR  - R21 AG059217/AG/NIA NIH HHS/United States
GR  - R01 AG038710/AG/NIA NIH HHS/United States
GR  - R01 AG021173/AG/NIA NIH HHS/United States
GR  - R21 AG048519/AG/NIA NIH HHS/United States
GR  - R01 AG044420/AG/NIA NIH HHS/United States
GR  - RF1 AG056114/AG/NIA NIH HHS/United States
GR  - RF1 AG044420/AG/NIA NIH HHS/United States
GR  - R01 NS046673/NS/NINDS NIH HHS/United States
GR  - RF1 AG056130/AG/NIA NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Rep
JT  - Cell reports
JID - 101573691
RN  - 0 (Cdk5r1 protein, mouse)
RN  - 0 (Men1 protein, mouse)
RN  - 0 (Proto-Oncogene Proteins)
RN  - EC 2.7.- (Phosphotransferases)
SB  - IM
MH  - Animals
MH  - Cognitive Dysfunction/complications/*genetics/*physiopathology
MH  - Gene Expression Regulation
MH  - Genetic Loci
MH  - Memory Disorders/complications/physiopathology
MH  - Mice, Knockout
MH  - Neurons/*metabolism
MH  - Organ Specificity
MH  - Phosphotransferases/*genetics/metabolism
MH  - Promoter Regions, Genetic/genetics
MH  - Proto-Oncogene Proteins/*deficiency/metabolism
MH  - Synapses/*metabolism/pathology
MH  - Transcription, Genetic
PMC - PMC6434950
MID - NIHMS1011724
OTO - NOTNLM
OT  - Cdk5
OT  - cognition
OT  - menin
OT  - p35
OT  - synaptic function
COIS- Declaration of Interests The authors declare no competing interests
EDAT- 2018/07/19 06:00
MHDA- 2019/12/04 06:00
PMCR- 2019/03/26
CRDT- 2018/07/19 06:00
PHST- 2018/01/07 00:00 [received]
PHST- 2018/05/03 00:00 [revised]
PHST- 2018/06/12 00:00 [accepted]
PHST- 2018/07/19 06:00 [entrez]
PHST- 2018/07/19 06:00 [pubmed]
PHST- 2019/12/04 06:00 [medline]
PHST- 2019/03/26 00:00 [pmc-release]
AID - S2211-1247(18)30965-3 [pii]
AID - 10.1016/j.celrep.2018.06.055 [doi]
PST - ppublish
SO  - Cell Rep. 2018 Jul 17;24(3):701-712. doi: 10.1016/j.celrep.2018.06.055.