Skip to main content

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: â–² Purine metabolism

      

IPA: â–² Concentration of ATP

 

Hypoxanthine-guanine phosphoribosyltransferase

P00493

Hprt1

3

5|4

not significant

 

4|4

1.24

â–²

0.0054

0.018

 
 

1

4|5

 

6|4

1.22

â–²

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

â–²

3.5 × 10-05

4.4 × 10-04

 

5|7

1.15

â–²

<×10-16

<×10-16

 
 

1

5|7

1.12

â–²

8.9 × 10-16

1.1 × 10-14

 

5|5

1.18

â–²

1.2 × 10-07

7.1 × 10-07

 
 

Pyruvate kinase, mito.

P52480

Pkm

3

4|5

1.17

â–²

0.0007

0.0059

 

4|5

1.26

â–²

1.3 × 10-06

8.3 × 10-06

â–²***

 

2

5|7

1.13

â–²

1.4 × 10-08

1.6 × 10-07

 

4|7

1.07

â–²

0.0028

0.0158

 

NADH-ubiquinone oxidoreductase 75 kDa subunit, mito.

Q91VD9

Ndufs1

1

4|4

1.18

â–²

0.001

0.005

 

8|4

1.28

â–²

<×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

â–²

0.0004

0.0015

 

3|4

not significant

 
 

Vesicular glutamate transporter 1 (VGluT1)

Q3TXX4

Slc17a7

3

5

1.14

â–²

0.0031

0.0192

 

5

not significant

 
 

1

6

1.20

â–²

<×10-16

<×10-16

 

4|6

not significant

 
 

4-aminobutyrate aminotransferase, mito

P61922

Abat

2

4|6

1.14

â–²

0.0006

0.0024

 

4|5

not significant

 

Clathrin-mediated exo-/endocytosis

               
 

Pathway analysis (LC-MSE)

   

PSEA: â–² Vesicle coating, â–² Membrane budding

 

not annotated

 
    

PSEA: â–² Clathrin coated pit etc.

  
    

IPA: â–² Formation of artificial clathrin cages

  
 

AP-2 complex subunit alpha-1

P17426

Ap2a1

1

5|6

1.13

â–²

6.5 × 10-08

5.2 × 10-07

 

6|6

not significant

â–²*

 

Synaptojanin

Q8CHC4

Synj

2

3|5|3

1.08

â–²

0.017

0.041

 

5|5|5

not significant

 
 

Synapsin-1

O88935

Syn1

2

6|4|3

1.11

â–²

0.005

0.016

 

6|4|3

not significant

 
 

Synaptotagmin-1

P46096

Syt1

2

6|7

1.09

â–²

0.001

0.004

 

5|6

1.11

â–²

0.0016

0.0112

â–²**

Neurotransmitter receptors

               
 

N-methyl-D-aspartate receptor subunit NR1

P35438

Grin1

3

6

0.26

â–¼

<×10-16

<×10-16

 

3|2

0.16

â–¼

<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: â–¼ Long term potentiation (of synapse)

IPA: â–¼ Long term potentiation

    

PSEA: â–¼ Long term potentiation

 
    

PSEA: â–¼ EBB-signalling pathway

  
 

CaM kinase II subunit alpha

P11798

Camk2a

3

3|4

0.90

â–¼

0.0006

0.0056

â–¼***

3|5

not significant

â–¼*

 

CaM kinase II subunit beta

P28652

Camk2b

1

6|6

not significant

 

6|6

0.89

â–¼

1.5 × 10-08

1.2 × 10-07

 
 

2

6|6

 

6|6

0.96

â–¼

3.6 × 10-05

1.7 × 10-04

 
 

3

5|4

 

6|7

0.89

â–¼

1.5 × 10-08

1.2 × 10-07

 
 

CaM kinase II subunit gamma

Q923T9

Camk2g

3

4|4

not significant

â–¼***

4|4

not significant

 
 

Calcineurin subunit B type 1

Q63810

Ppp3r1

2

6|6

0.90

â–¼

0.0002

0.001

 

7|6

not significant

 
 

Ser/thr-protein phosphatase 2B cat. subunit β

P48453

Ppp3cb

2

5|2

1.11

â–²

0.012

0.032

 

5|2

not significant

 
 

Neurochondrin

Q9Z0E0

Ncdn

3

4|3

1.21

â–²

0.017

0.083

 

4|4

not significant

 
 

1

4|3

1.16

â–²

0.001

0.005

 

3|3

â–¼**

 

Disks large homolog 4 (PSD-95)

Q62108

Dlg4

3

5|4

not significant

 

4|5

1.18

â–²

0.0004

0.0015

 
 

1

4|3

1.15

â–²

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

â–²

0.10

0.33

 

6|4

1.12

â–²

0.007

0.021

â–²(*)

 

1

8

1.12

â–²

0.001

0.005

 

8|9

1.20

â–²

<×10-16

<×10-16

 
 

Mitogen-activated protein kinase 1 (ERK-2 )

P63085

Erk2

3

5|5

1.07

â–²

0.04

0.13

 

6|5

1.12

â–²

0.0002

0.0009

 
 

2

4|6|6

1.16

â–²

9.8 × 10-10

1.7 × 10-08

 

4|6|6

0.94

â–²

0.0202

0.0685

 
 

Mitogen-activated protein kinase 3 (ERK-1)

Q63844

Erk1

3

4|4|4

1.10

â–²

0.03

0.11

 

4|4|4

1.14

â–²

0.0004

0.0015

 

Actin cytoskeleton/cell morphology/structural elements

         
 

Pathway analysis (LC-MSE)

amongst others:

 

IPA: â–¼ Organisation of cytoskeleton

IPA: â–² Formation plasma membrane projections

    

IPA: â–¼ Organisation of cytoplasm

IPA: â–² Microtubuli dynamics

    

IPA: Degeneration of axons

IPA: â–² Organisation of cytoskeleton

    

PSEA: â–² Neuronal projection membrane

IPA: â–²Organisation of cellular protrusions

     

PSEA: â–² Regulation of synaptic plasticity

     

PSEA: â–² Neg. regulation of cell differentiation

     

PSEA: â–² Neg. regulation of cell death/apoptosis

     

PSEA: â–¼ Extracellular matrix/space

 

Myristoylated alanine-rich C-kinase substrate

P26645

Marcks

2

6|2|4

1.22

â–²

8.4 × 10-05

5.7 × 10-04

â–²***

4|4|6

1.41

â–²

1.1 × 10-08

1.1 × 10-07

â–²(*)

 

3

4|4|6

not significant

6|3|4

1.32

â–²

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

â–²

2.9 × 10-09

3.6 × 10-08

â–¼**

 

Methionine aminopeptidase 2 (MAP 2)

O08663

Metap2

3

5|4

not significant

 

5|3

1.28

â–²

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

â–²

0.0010

0.0086

 
 

Vesicle-fusing ATPase

P46460

Nsf

3

5|6|6

1.07

â–²

0.008

0.047

 

5|6|5

1.10

â–²

0.0005

0.0018

 
 

2

6|5|4

1.10

â–²

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

â–²

0.008

0.022

 

6

1.21

â–²

0.008

0.038

 
 

Neural cell adhesion molecule 1 (N-CAM-1)

P13595

Ncam1

2

6|5|3

1.11

â–²

0.0003

0.001

 

6|5|3

1.11

â–²

0.0003

0.003

 
 

2’,3’-cyclic-nucleotide 3’-phosphodiesterase (CNPase)

P16330

Cnp

3

5|3|3

0.84

â–¼

0.024

0.108

 

4|3|5

not significant

â–¼*

 

Myelin basic protein (MBP)

P04370

Mbp

3

5

0.87

â–¼

1.7 × 10-05

0.0003

 

5

not significant

 
 

2

5

not significant

 

5

0.93

â–¼

0.0127

0.0479

 
 

Myelin proteolipid protein (PLP)

P60202

Plp1

3

5|4|4

0.87

â–¼

1.2 × 10-07

3.0 × 10-06

â–¼***

5|4|4

1.11

â–²

0.0001

0.0005

â–¼*

 

2

6|7|7

0.87

â–¼

<×10-16

<×10-16

6|7|6

0.96

â–¼

0.0123

0.0479

 

Glial fibrillary acidic protein (GFAP)

P03995

Gfap

3

3|4

1.23

â–²

0.002

0.017

 

3|4

1.29

â–²

1.8 × 10-06

9.9 × 10-06

â–²*

 

Coronin-1A (Coronin-like protein A)

O89053

Coro1a

1

5|5

1.11

â–²

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].