PMID- 19401593
OWN - NLM
STAT- MEDLINE
DCOM- 20090925
LR  - 20220129
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 2
IP  - 68
DP  - 2009 Apr 28
TI  - Neurotransmitters drive combinatorial multistate postsynaptic density networks.
PG  - ra19
LID - 10.1126/scisignal.2000102 [doi]
AB  - The mammalian postsynaptic density (PSD) comprises a complex collection of 
      approximately 1100 proteins. Despite extensive knowledge of individual proteins, 
      the overall organization of the PSD is poorly understood. Here, we define maps of 
      molecular circuitry within the PSD based on phosphorylation of postsynaptic 
      proteins. Activation of a single neurotransmitter receptor, the 
      N-methyl-D-aspartate receptor (NMDAR), changed the phosphorylation status of 127 
      proteins. Stimulation of ionotropic and metabotropic glutamate receptors and 
      dopamine receptors activated overlapping networks with distinct combinatorial 
      phosphorylation signatures. Using peptide array technology, we identified 
      specific phosphorylation motifs and switching mechanisms responsible for the 
      integration of neurotransmitter receptor pathways and their coordination of 
      multiple substrates in these networks. These combinatorial networks confer high 
      information-processing capacity and functional diversity on synapses, and their 
      elucidation may provide new insights into disease mechanisms and new 
      opportunities for drug discovery.
FAU - Coba, Marcelo P
AU  - Coba MP
AD  - Genes to Cognition, Wellcome Trust Sanger Institute, Cambridgeshire, UK.
FAU - Pocklington, Andrew J
AU  - Pocklington AJ
FAU - Collins, Mark O
AU  - Collins MO
FAU - Kopanitsa, Maksym V
AU  - Kopanitsa MV
FAU - Uren, Rachel T
AU  - Uren RT
FAU - Swamy, Sajani
AU  - Swamy S
FAU - Croning, Mike D R
AU  - Croning MD
FAU - Choudhary, Jyoti S
AU  - Choudhary JS
FAU - Grant, Seth G N
AU  - Grant SG
LA  - eng
GR  - 066717/WT_/Wellcome Trust/United Kingdom
GR  - G0801418/MRC_/Medical Research Council/United Kingdom
GR  - G90/93/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20090428
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteome)
RN  - 0 (Receptors, Neurotransmitter)
RN  - 6384-92-5 (N-Methylaspartate)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Binding Sites
MH  - Chromatography, Liquid
MH  - Excitatory Amino Acid Agonists/pharmacology
MH  - Hippocampus/drug effects/*metabolism
MH  - Immunoblotting
MH  - In Vitro Techniques
MH  - Mass Spectrometry
MH  - Mice
MH  - Mice, Inbred Strains
MH  - Molecular Sequence Data
MH  - N-Methylaspartate/pharmacology
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation/drug effects
MH  - Protein Array Analysis
MH  - Protein Binding
MH  - Proteome/*metabolism
MH  - Proteomics/methods
MH  - Receptors, Neurotransmitter/*metabolism
MH  - Signal Transduction/drug effects
MH  - Synapses/*metabolism
MH  - Synaptic Transmission/drug effects
PMC - PMC3280897
MID - UKMS36018
OID - NLM: UKMS36018
EDAT- 2009/04/30 09:00
MHDA- 2009/09/26 06:00
PMCR- 2012/02/16
CRDT- 2009/04/30 09:00
PHST- 2009/04/30 09:00 [entrez]
PHST- 2009/04/30 09:00 [pubmed]
PHST- 2009/09/26 06:00 [medline]
PHST- 2012/02/16 00:00 [pmc-release]
AID - 2/68/ra19 [pii]
AID - 10.1126/scisignal.2000102 [doi]
PST - epublish
SO  - Sci Signal. 2009 Apr 28;2(68):ra19. doi: 10.1126/scisignal.2000102.