PMID- 25944900
OWN - NLM
STAT- MEDLINE
DCOM- 20151002
LR  - 20211203
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 290
IP  - 26
DP  - 2015 Jun 26
TI  - Mammalian Target of Rapamycin (mTOR) Tagging Promotes Dendritic Branch 
      Variability through the Capture of Ca2+/Calmodulin-dependent Protein Kinase II alpha 
      (CaMKIIalpha) mRNAs by the RNA-binding Protein HuD.
PG  - 16357-71
LID - 10.1074/jbc.M114.599399 [doi]
AB  - The fate of a memory, whether stored or forgotten, is determined by the ability 
      of an active or tagged synapse to undergo changes in synaptic efficacy requiring 
      protein synthesis of plasticity-related proteins. A synapse can be tagged, but 
      without the "capture" of plasticity-related proteins, it will not undergo long 
      lasting forms of plasticity (synaptic tagging and capture hypothesis). What the 
      "tag" is and how plasticity-related proteins are captured at tagged synapses are 
      unknown. Ca(2+)/calmodulin-dependent protein kinase II alpha (CaMKIIalpha) is critical in 
      learning and memory and is synthesized locally in neuronal dendrites. The 
      mechanistic (mammalian) target of rapamycin (mTOR) is a protein kinase that 
      increases CaMKIIalpha protein expression; however, the mechanism and site of 
      dendritic expression are unknown. Herein, we show that mTOR activity mediates the 
      branch-specific expression of CaMKIIalpha, favoring one secondary, daughter branch 
      over the other in a single neuron. mTOR inhibition decreased the dendritic levels 
      of CaMKIIalpha protein and mRNA by shortening its poly(A) tail. Overexpression of the 
      RNA-stabilizing protein HuD increased CaMKIIalpha protein levels and preserved its 
      selective expression in one daughter branch over the other when mTOR was 
      inhibited. Unexpectedly, deleting the third RNA recognition motif of HuD, the 
      domain that binds the poly(A) tail, eliminated the branch-specific expression of 
      CaMKIIalpha when mTOR was active. These results provide a model for one molecular 
      mechanism that may underlie the synaptic tagging and capture hypothesis where 
      mTOR is the tag, preventing deadenylation of CaMKIIalpha mRNA, whereas HuD captures 
      and promotes its expression in a branch-specific manner.
CI  - (c) 2015 by The American Society for Biochemistry and Molecular Biology, Inc.
FAU - Sosanya, Natasha M
AU  - Sosanya NM
AD  - From the Center for Learning and Memory, Department of Neuroscience, Institute 
      for Cell Biology, and United States Army Institute of Surgical Research, Joint 
      Base San Antonio-Fort Sam, Houston, Texas 78234, and.
FAU - Cacheaux, Luisa P
AU  - Cacheaux LP
AD  - From the Center for Learning and Memory, Department of Neuroscience.
FAU - Workman, Emily R
AU  - Workman ER
AD  - From the Center for Learning and Memory, Department of Neuroscience, Institute 
      for Neuroscience, University of Texas, Austin, Texas 78712.
FAU - Niere, Farr
AU  - Niere F
AD  - From the Center for Learning and Memory, Department of Neuroscience.
FAU - Perrone-Bizzozero, Nora I
AU  - Perrone-Bizzozero NI
AD  - Department of Neurosciences, Psychiatry and Behavioral Sciences, University of 
      New Mexico Health Sciences Center, Albuquerque, New Mexico 87131.
FAU - Raab-Graham, Kimberly F
AU  - Raab-Graham KF
AD  - From the Center for Learning and Memory, Department of Neuroscience, Institute 
      for Cell Biology, and Institute for Neuroscience, University of Texas, Austin, 
      Texas 78712, Kimberly@mail.clm.utexas.edu.
LA  - eng
GR  - R01 NS030255/NS/NINDS NIH HHS/United States
GR  - DA034897/DA/NIDA NIH HHS/United States
GR  - R01 NS30255/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20150505
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (ELAV Proteins)
RN  - 0 (ELAV-Like Protein 4)
RN  - 0 (Elavl4 protein, rat)
RN  - 0 (RNA, Messenger)
RN  - EC 2.7.1.1 (mTOR protein, rat)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - EC 2.7.11.17 (Camk2a protein, rat)
SB  - IM
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/*metabolism
MH  - Dendrites/enzymology/genetics/*metabolism
MH  - ELAV Proteins/genetics/*metabolism
MH  - ELAV-Like Protein 4
MH  - Hippocampus/cytology/enzymology/metabolism
MH  - Neurons/metabolism
MH  - Protein Binding
MH  - RNA, Messenger/genetics/*metabolism
MH  - Rats
MH  - Synapses/enzymology/genetics/metabolism
MH  - TOR Serine-Threonine Kinases/genetics/*metabolism
PMC - PMC4481233
OTO - NOTNLM
OT  - RNA-binding protein
OT  - dendritic branch
OT  - fluorescence
OT  - in situ hybridization
OT  - mRNA decay
OT  - mammalian target of rapamycin (mTOR)
OT  - neuron
OT  - protein synthesis
OT  - synaptic tagging and capture
OT  - translational control
EDAT- 2015/05/07 06:00
MHDA- 2015/10/03 06:00
PMCR- 2016/06/26
CRDT- 2015/05/07 06:00
PHST- 2014/07/28 00:00 [received]
PHST- 2015/05/07 06:00 [entrez]
PHST- 2015/05/07 06:00 [pubmed]
PHST- 2015/10/03 06:00 [medline]
PHST- 2016/06/26 00:00 [pmc-release]
AID - S0021-9258(20)58461-5 [pii]
AID - M114.599399 [pii]
AID - 10.1074/jbc.M114.599399 [doi]
PST - ppublish
SO  - J Biol Chem. 2015 Jun 26;290(26):16357-71. doi: 10.1074/jbc.M114.599399. Epub 
      2015 May 5.