PMID- 19240035
OWN - NLM
STAT- MEDLINE
DCOM- 20090618
LR  - 20211020
IS  - 0021-9258 (Print)
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 284
IP  - 16
DP  - 2009 Apr 17
TI  - beta-Amyloid impairs AMPA receptor trafficking and function by reducing 
      Ca2+/calmodulin-dependent protein kinase II synaptic distribution.
PG  - 10639-49
LID - 10.1074/jbc.M806508200 [doi]
AB  - A fundamental feature of Alzheimer disease (AD) is the accumulation of 
      beta-amyloid (Abeta), a peptide generated from the amyloid precursor protein 
      (APP). Emerging evidence suggests that soluble Abeta oligomers adversely affect 
      synaptic function, which leads to cognitive failure associated with AD. The 
      Abeta-induced synaptic dysfunction has been attributed to the synaptic removal of 
      alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors 
      (AMPARs); however, it is unclear how Abeta induces the loss of AMPARs at the 
      synapses. In this study we have examined the potential involvement of 
      Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), a signaling molecule 
      critical for AMPAR trafficking and function. We found that the synaptic pool of 
      CaMKII was significantly decreased in cortical neurons from APP transgenic mice, 
      and the density of CaMKII clusters at synapses was significantly reduced by Abeta 
      oligomer treatment. In parallel, the surface expression of GluR1 subunit as well 
      as AMPAR-mediated synaptic response and ionic current was selectively decreased 
      in APP transgenic mice and Abeta-treated cultures. Moreover, the reducing effect 
      of Abeta on AMPAR current density was mimicked and occluded by knockdown of 
      CaMKII and blocked by overexpression of CaMKII. These results suggest that the 
      Abeta-induced change in CaMKII subcellular distribution may underlie the removal 
      of AMPARs from synaptic membrane by Abeta.
FAU - Gu, Zhenglin
AU  - Gu Z
AD  - Department of Physiology and Biophysics, State University of New York, School of 
      Medicine and Biomedical Sciences, Buffalo, New York 14214, USA.
FAU - Liu, Wenhua
AU  - Liu W
FAU - Yan, Zhen
AU  - Yan Z
LA  - eng
GR  - AG21923/AG/NIA NIH HHS/United States
GR  - MH84233/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090224
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Amyloid beta-Protein Precursor)
RN  - 0 (NR1 NMDA receptor)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 77521-29-0 (alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinase Type 2)
RN  - TFZ3H25BS1 (glutamate receptor ionotropic, AMPA 1)
SB  - IM
MH  - Amyloid beta-Peptides/genetics/*metabolism
MH  - Amyloid beta-Protein Precursor/genetics/metabolism
MH  - Animals
MH  - Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics/*metabolism
MH  - Cells, Cultured
MH  - Cerebral Cortex/cytology
MH  - Female
MH  - Male
MH  - Mice
MH  - Mice, Transgenic
MH  - RNA, Small Interfering/genetics/metabolism
MH  - Receptors, AMPA/genetics/*metabolism
MH  - Receptors, N-Methyl-D-Aspartate/genetics/*metabolism
MH  - Signal Transduction/physiology
MH  - Synapses/*metabolism/ultrastructure
MH  - Synaptic Transmission/physiology
MH  - alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism
PMC - PMC2667751
EDAT- 2009/02/26 09:00
MHDA- 2009/06/19 09:00
PMCR- 2010/04/17
CRDT- 2009/02/26 09:00
PHST- 2009/02/26 09:00 [entrez]
PHST- 2009/02/26 09:00 [pubmed]
PHST- 2009/06/19 09:00 [medline]
PHST- 2010/04/17 00:00 [pmc-release]
AID - S0021-9258(20)39906-3 [pii]
AID - 10639 [pii]
AID - 10.1074/jbc.M806508200 [doi]
PST - ppublish
SO  - J Biol Chem. 2009 Apr 17;284(16):10639-49. doi: 10.1074/jbc.M806508200. Epub 2009 
      Feb 24.