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Table 2 Significantly changed proteins identified using label-based LC-SRM in the frontal cortex and hippocampus of the NR1 neo−/− (n = 12) compared to wildtype mice (n = 12)

From: Integrative proteomic analysis of the NMDA NR1 knockdown mouse model reveals effects on central and peripheral pathways associated with schizophrenia and autism spectrum disorders

     Frontal Cortex Hippocampus
Biological Pathway/Function UP-ID Gene name M TPP Ratio NR1/Wt P P* LC-MSE TPP Ratio NR1/Wt P P* LC-MSE
Purine metabolism                
  Pathway analysis (LC-MSE)      not annotated   PSEA: ▲ Purine metabolism
       IPA: ▲ Concentration of ATP
  Hypoxanthine-guanine phosphoribosyltransferase P00493 Hprt1 3 5|4 not significant   4|4 1.24 ▲ 0.0054 0.018  
  1 4|5   6|4 1.22 ▲ 1.8 × 10-15 1.4 × 10-14  
Glycolysis/Gluconeogenesis/Tricarbon acid cycle               
  Pathway analysis (LC-MSE)          IPA: Metabolism of NADH
       PSEA: TCA cycle
  Aspartate aminotransferase, mito. P05202 Got2 3 5|4 1.15 ▲ 3.5 × 10-05 4.4 × 10-04   5|7 1.15 ▲ <×10-16 <×10-16  
  1 5|7 1.12 ▲ 8.9 × 10-16 1.1 × 10-14   5|5 1.18 ▲ 1.2 × 10-07 7.1 × 10-07  
  Pyruvate kinase, mito. P52480 Pkm 3 4|5 1.17 ▲ 0.0007 0.0059   4|5 1.26 ▲ 1.3 × 10-06 8.3 × 10-06 ▲***
  2 5|7 1.13 ▲ 1.4 × 10-08 1.6 × 10-07   4|7 1.07 ▲ 0.0028 0.0158
  NADH-ubiquinone oxidoreductase 75 kDa subunit, mito. Q91VD9 Ndufs1 1 4|4 1.18 ▲ 0.001 0.005   8|4 1.28 ▲ <×10-16 <×10-16  
Neurotransmitter metabolism/transport                
  Pathway analysis (LC-MSE)     IPA: Transport of amino acids   not annotated  
     IPA: Transport of L-glutamic acid   
  Proline dehydrogenase 1, mito. Q9WU79 Prodh 3 5|4 not significant   2|2 not significant  
  1 2|2   4|3  
  Catechol O-methyltransferase O88587 Comt 1 4|2 not significant   3|3 not significant  
  Glutamate decarboxylase 2 P48320 Gad2 2 3|4 1.25 ▲ 0.0004 0.0015   3|4 not significant  
  Vesicular glutamate transporter 1 (VGluT1) Q3TXX4 Slc17a7 3 5 1.14 ▲ 0.0031 0.0192   5 not significant  
  1 6 1.20 ▲ <×10-16 <×10-16   4|6 not significant  
  4-aminobutyrate aminotransferase, mito P61922 Abat 2 4|6 1.14 ▲ 0.0006 0.0024   4|5 not significant  
Clathrin-mediated exo-/endocytosis                
  Pathway analysis (LC-MSE)     PSEA: ▲ Vesicle coating, ▲ Membrane budding   not annotated  
     PSEA: ▲ Clathrin coated pit etc.   
     IPA: ▲ Formation of artificial clathrin cages   
  AP-2 complex subunit alpha-1 P17426 Ap2a1 1 5|6 1.13 ▲ 6.5 × 10-08 5.2 × 10-07   6|6 not significant ▲*
  Synaptojanin Q8CHC4 Synj 2 3|5|3 1.08 ▲ 0.017 0.041   5|5|5 not significant  
  Synapsin-1 O88935 Syn1 2 6|4|3 1.11 ▲ 0.005 0.016   6|4|3 not significant  
  Synaptotagmin-1 P46096 Syt1 2 6|7 1.09 ▲ 0.001 0.004   5|6 1.11 ▲ 0.0016 0.0112 ▲**
Neurotransmitter receptors                
  N-methyl-D-aspartate receptor subunit NR1 P35438 Grin1 3 6 0.26 ▼ <×10-16 <×10-16   3|2 0.16 ▼ <E-16 <E-16  
  Glutamate receptor 1 (GluR-1) P23818 Gria1 3 4|3 not significant   4 not significant  
  Glutamate receptor 2 (GluR-2) P23819 Gria2 3 5|4|4|4 not significant   4|3 not significant  
  Glutamate receptor 3 (GluR-3) Q9Z2W9 Gria3 3 4|2 not significant   3|4|3|4 not significant  
Long-term potentiation/Signal transduction                
  Pathway analysis (LC-MSE)     IPA: ▼ Long term potentiation (of synapse) IPA: ▼ Long term potentiation
     PSEA: ▼ Long term potentiation  
     PSEA: ▼ EBB-signalling pathway   
  CaM kinase II subunit alpha P11798 Camk2a 3 3|4 0.90 ▼ 0.0006 0.0056 ▼*** 3|5 not significant ▼*
  CaM kinase II subunit beta P28652 Camk2b 1 6|6 not significant   6|6 0.89 ▼ 1.5 × 10-08 1.2 × 10-07  
  2 6|6   6|6 0.96 ▼ 3.6 × 10-05 1.7 × 10-04  
  3 5|4   6|7 0.89 ▼ 1.5 × 10-08 1.2 × 10-07  
  CaM kinase II subunit gamma Q923T9 Camk2g 3 4|4 not significant ▼*** 4|4 not significant  
  Calcineurin subunit B type 1 Q63810 Ppp3r1 2 6|6 0.90 ▼ 0.0002 0.001   7|6 not significant  
  Ser/thr-protein phosphatase 2B cat. subunit β P48453 Ppp3cb 2 5|2 1.11 ▲ 0.012 0.032   5|2 not significant  
  Neurochondrin Q9Z0E0 Ncdn 3 4|3 1.21 ▲ 0.017 0.083   4|4 not significant  
  1 4|3 1.16 ▲ 0.001 0.005   3|3 ▼**
  Disks large homolog 4 (PSD-95) Q62108 Dlg4 3 5|4 not significant   4|5 1.18 ▲ 0.0004 0.0015  
  1 4|3 1.15 ▲ 0.0032 0.0099   4|3 not significant  
ERK-Pathway                
  Pathway analysis     IPA: Implicated in top network IPA: Implicated in top network
  Astrocytic phosphoprotein PEA-15 Q62048 Pea15 3 5|4 1.09 ▲ 0.10 0.33   6|4 1.12 ▲ 0.007 0.021 ▲(*)
  1 8 1.12 ▲ 0.001 0.005   8|9 1.20 ▲ <×10-16 <×10-16  
  Mitogen-activated protein kinase 1 (ERK-2 ) P63085 Erk2 3 5|5 1.07 ▲ 0.04 0.13   6|5 1.12 ▲ 0.0002 0.0009  
  2 4|6|6 1.16 ▲ 9.8 × 10-10 1.7 × 10-08   4|6|6 0.94 ▲ 0.0202 0.0685  
  Mitogen-activated protein kinase 3 (ERK-1) Q63844 Erk1 3 4|4|4 1.10 ▲ 0.03 0.11   4|4|4 1.14 ▲ 0.0004 0.0015  
Actin cytoskeleton/cell morphology/structural elements          
  Pathway analysis (LC-MSE) amongst others:   IPA: ▼ Organisation of cytoskeleton IPA: ▲ Formation plasma membrane projections
     IPA: ▼ Organisation of cytoplasm IPA: ▲ Microtubuli dynamics
     IPA: Degeneration of axons IPA: ▲ Organisation of cytoskeleton
     PSEA: ▲ Neuronal projection membrane IPA: ▲Organisation of cellular protrusions
      PSEA: ▲ Regulation of synaptic plasticity
      PSEA: ▲ Neg. regulation of cell differentiation
      PSEA: ▲ Neg. regulation of cell death/apoptosis
      PSEA: ▼ Extracellular matrix/space
  Myristoylated alanine-rich C-kinase substrate P26645 Marcks 2 6|2|4 1.22 ▲ 8.4 × 10-05 5.7 × 10-04 ▲*** 4|4|6 1.41 ▲ 1.1 × 10-08 1.1 × 10-07 ▲(*)
  3 4|4|6 not significant 6|3|4 1.32 ▲ 2.3 × 10-10 8.0 × 10-09
  PKC and casein kinase substrate in neurons protein 1 Q61644 Pacsin1 3 6|4 not significant   6|3 1.28 ▲ 2.9 × 10-09 3.6 × 10-08 ▼**
  Methionine aminopeptidase 2 (MAP 2) O08663 Metap2 3 5|4 not significant   5|3 1.28 ▲ 1.6 × 10-07 1.1 × 10-06  
  Neurofilament light polypeptide (NF-L) P08551 Nefl 2 3|4|3 not significant   3|4|3 1.13 ▲ 0.0010 0.0086  
  Vesicle-fusing ATPase P46460 Nsf 3 5|6|6 1.07 ▲ 0.008 0.047   5|6|5 1.10 ▲ 0.0005 0.0018  
  2 6|5|4 1.10 ▲ 2.0 × 10-07 1.7 × 10-06   6|5|4 not significant  
  Neuromodulin (Axonal membrane protein GAP-43) P06837 Gap43 2 5|6 1.21 ▲ 0.008 0.022   6 1.21 ▲ 0.008 0.038  
  Neural cell adhesion molecule 1 (N-CAM-1) P13595 Ncam1 2 6|5|3 1.11 ▲ 0.0003 0.001   6|5|3 1.11 ▲ 0.0003 0.003  
  2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNPase) P16330 Cnp 3 5|3|3 0.84 ▼ 0.024 0.108   4|3|5 not significant ▼*
  Myelin basic protein (MBP) P04370 Mbp 3 5 0.87 ▼ 1.7 × 10-05 0.0003   5 not significant  
  2 5 not significant   5 0.93 ▼ 0.0127 0.0479  
  Myelin proteolipid protein (PLP) P60202 Plp1 3 5|4|4 0.87 ▼ 1.2 × 10-07 3.0 × 10-06 ▼*** 5|4|4 1.11 ▲ 0.0001 0.0005 ▼*
  2 6|7|7 0.87 ▼ <×10-16 <×10-16 6|7|6 0.96 ▼ 0.0123 0.0479
  Glial fibrillary acidic protein (GFAP) P03995 Gfap 3 3|4 1.23 ▲ 0.002 0.017   3|4 1.29 ▲ 1.8 × 10-06 9.9 × 10-06 ▲*
  Coronin-1A (Coronin-like protein A) O89053 Coro1a 1 5|5 1.11 ▲ 0.003 0.010   5|5 not significant  
  1. IPA, Ingenuity pathway analysis; PSEA, Protein set enrichment analysis; UP-ID, uniprot-ID; M, method (assays were split into three methods); TPP, transitions per peptide; G, specific for glutamatergic neurons; B, specific for GABA-ergic neurons; N, specific for neurons; O, oligodendrocyte specific; A, astrocyte specific; M, microglia specific; ▲, increased, ▼, decreased. *, **, and *** ≤0.05, 0.01, and 0.001, respectively. P values were determined using SRMstats and corrected (P*) to control for multiple hypothesis testing [37].
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Molecular Autism

ISSN: 2040-2392