PMID- 30181804
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 9
IP  - 63
DP  - 2018 Aug 14
TI  - Pumilio2 regulates synaptic plasticity via translational repression of synaptic 
      receptors in mice.
PG  - 32134-32148
LID - 10.18632/oncotarget.24345 [doi]
AB  - PUMILIO 2 (PUM2) is a member of Pumilio and FBF (PUF) family, an RNA binding 
      protein family with phylogenetically conserved roles in germ cell development. 
      The Drosophila Pumilio homolog is also required for dendrite morphogenesis and 
      synaptic function via translational control of synaptic proteins, such as 
      glutamate receptors, and recent mammalian studies demonstrated a similar role in 
      neuronal culture with associated motor and memory abnormalities in vivo. 
      Importantly, transgenic mice with PUM2 knockout show prominent epileptiform 
      activity, and patients with intractable temporal lobe epilepsy and mice with 
      pilocarpine-induced seizures have decreased neuronal PUM2, possibly leading to 
      further seizure susceptibility. However, how PUM2 influences synaptic function in 
      vivo and, subsequently, seizures is not known. We found that PUM2 is highly 
      expressed in the brain, especially in the temporal lobe, and knockout of Pum2 
      (Pum2(-/-) ) resulted in significantly increased pyramidal cell dendrite spine 
      and synapse density. In addition, multiple proteins associated with excitatory 
      synaptic function, including glutamate receptor 2 (GLUR2), are up-regulated in 
      Pum2(-/-) mice. The expression of GLUR2 protein but not mRNA is increased in the 
      Pum2(-/-) mutant hippocampus, Glur2 transcripts are increased in mutant polysome 
      fractions, and overexpression of PUM2 led to repression of reporter expression 
      containing the 3'Untranslated Region (3'UTR) of Glur2, suggesting translation of 
      GLUR2 was increased in the absence of Pum2. Overall, these studies provide a 
      molecular mechanism for the increased temporal lobe excitability observed with 
      PUM2 loss and suggest PUM2 might contribute to intractable temporal lobe 
      epilepsy.
FAU - Dong, Hongxin
AU  - Dong H
AD  - Departments of Psychiatry and Behavioral Sciences, Northwestern University 
      Feinberg School of Medicine, Chicago, IL 60611, USA.
FAU - Zhu, Mengyi
AU  - Zhu M
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, 211166, P. R. China.
FAU - Meng, Liping
AU  - Meng L
AD  - Departments of Psychiatry and Behavioral Sciences, Northwestern University 
      Feinberg School of Medicine, Chicago, IL 60611, USA.
FAU - Ding, Yan
AU  - Ding Y
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, 211166, P. R. China.
FAU - Yang, Ding
AU  - Yang D
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, 211166, P. R. China.
FAU - Zhang, Shanshan
AU  - Zhang S
AD  - Departments of Psychiatry and Behavioral Sciences, Northwestern University 
      Feinberg School of Medicine, Chicago, IL 60611, USA.
FAU - Qiang, Wenan
AU  - Qiang W
AD  - Department of Obstetrics and Gynecology, Northwestern University Feinberg School 
      of Medicine, Chicago, IL 60611, USA.
FAU - Fisher, Daniel W
AU  - Fisher DW
AD  - Department of Neurology, Northwestern University Feinberg School of Medicine, 
      Chicago, IL 60611, USA.
FAU - Xu, Eugene Yujun
AU  - Xu EY
AD  - State Key Laboratory of Reproductive Medicine, Nanjing Medical University, 
      Nanjing, 211166, P. R. China.
LA  - eng
GR  - R01 MH109466/MH/NIMH NIH HHS/United States
GR  - R21 MH100919/MH/NIMH NIH HHS/United States
GR  - U01 HD045871/HD/NICHD NIH HHS/United States
GR  - U54 CA193419/CA/NCI NIH HHS/United States
PT  - Journal Article
DEP - 20180130
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC6114944
OTO - NOTNLM
OT  - Pumilio (PUM)
OT  - RNA binding protein
OT  - dendrite
OT  - glutamate receptor 2 (GLUR2)
OT  - synapse
COIS- CONFLICTS OF INTEREST None declared.
EDAT- 2018/09/06 06:00
MHDA- 2018/09/06 06:01
PMCR- 2018/08/14
CRDT- 2018/09/06 06:00
PHST- 2017/08/23 00:00 [received]
PHST- 2018/01/13 00:00 [accepted]
PHST- 2018/09/06 06:00 [entrez]
PHST- 2018/09/06 06:00 [pubmed]
PHST- 2018/09/06 06:01 [medline]
PHST- 2018/08/14 00:00 [pmc-release]
AID - 24345 [pii]
AID - 10.18632/oncotarget.24345 [doi]
PST - epublish
SO  - Oncotarget. 2018 Jan 30;9(63):32134-32148. doi: 10.18632/oncotarget.24345. 
      eCollection 2018 Aug 14.