Table 2. Significantly changed proteins identified using label-based LC-SRM (targeted proteomics) in the PFC and HPC of the Df(16)A +/− mouse compared with wild-type mice (PFC=20 vs 20, HPC=11 vs 10).
|
Prefrontal cortex |
Hippocampus |
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|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Proteomics |
Proteomics |
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|
Discovery (D) |
Targeted proteomics (SRM) |
D |
Targeted proteomics (SRM) |
|||||||||||||||
| Transcriptomics | 10 vs 10 | 12 vs 10 | 20 vs 20 | 20 vs 21 | Transcriptomics | 10 vs 10 | 11 vs 10 | |||||||||||
| Uniprot | Acc. no. | Protein | Gene | Label | Ratio | P | P* | Ratio | P | P* | ||||||||
| 22q11.2 critical gene products+vector construct | ||||||||||||||||||
| Sep-05 | Q9Z2Q6 | Septin-5 | Sep-05 | 22q11.2 | ⇓ | ▾ | ▾ | ▾ | ▾ | 0.78 | 5.2E-11 | 1.1E-09 | ⇓ | ▾ | ▾ | 0.85 | 1.8E-04 | 4.9E-04 |
| RANG | P34022 | Ran-specific GTPase-activating protein | Ranbp1 | 22q11.2 | ⇓ | — | — | — | ▾ | 0.55 | <E-15 | <E-15 | ⇓ | — | ▾ | 0.47 | <E-15 | <E-15 |
| Q8JZU2 | Q8JZU2 | Protein Slc25a1 | Slc25a1 | 22q11.2 | ⇓ | — | — | — | ▾ | 0.79 | 4.8E-08 | 7.5E-07 | ⇓ | — | ▾ | 0.64 | 6.7E-10 | 5.9E-09 |
| PROD | Q9WU79 | Proline dehydrogenase 1, mitochondrial | Prodh | 22q11.2 | ⇓ | — | — | — | ▾ | 0.62 | 3.5E-07 | 4.4E-06 | ⇓ | — | ▾ | 0.90 | 0.26 | 0.30 |
| COMT | O88587 | Catechol O-methyltransferase | Comt | 22q11.2 | ⇓ | — | — | — | ▾ | 0.76 | 1.4E-06 | 1.4E-05 | ⇓ | — | ▾ | 0.71 | 1.6E-03 | 3.6E-03 |
| HPRT | P00493 | Hypoxanthine-guanine phosphoribosyltransferase | Hprt1 | Vector construct | * | ▴ | — | — | ▴ | 1.56 | <E-15 | <E-15 | — | — | ▾ | 1.77 | <E-15 | <E-15 |
| miRNA targets | ||||||||||||||||||
| GSK3B | Q9WV60 | Glycogen synthase kinase-3 beta | Gsk3b | miRNA target (2/4) | ⇑ | NS | — | ▾ | ▴ | 1.14 | 4E-06 | 3.2E-05 | NS | — | ▴ | 1.16 | 6.1E-04 | 1.5E-03 |
| OGT1 | Q8CGY8 | O-GlcNAc transferase subunit p110 | Ogt | miRNA target (1/4) + Figure 1d | ⇑ | ▴ | — | — | ▴ | 1.22 | 1.3E-02 | 3.5E-02 | NS | — | ▴ | 1.20 | 8.9E-03 | 1.6E-02 |
| KIF5A | P33175 | Kinesin heavy chain isoform 5A | Kif5a | miRNA target (1/4) | NS | — | — | ▴ | ▴ | 1.22 | 3.6E-02 | 0.09 | ⇑ | — | NS | 1.15 | 0.18 | 0.22 |
| A4 | P12023 | Amyloid beta A4 protein | App | miRNA target (1/4) | NS | — | — | — | NS | 1.13 | 6.5E-02 | 0.13 | NS | — | NS | 1.11 | 0.16 | 0.21 |
| KDM2A | P59997 | Lysine-specific demethylase 2A | Kdm2a | miRNA target (2/4) | NS | — | — | — | NS | 1.02 | 0.77 | 0.86 | NS | — | NS | 1.06 | 0.71 | 0.74 |
| RHOA | Q9QUI0 | Transforming protein RhoA | Rhoa | miRNA target, Liu et al.,115 | NS | NS | NS | NS | NS | 1.05 | 0.37 | 0.48 | NS | ▾ | NS | 1.08 | 0.05 | 0.08 |
| MBOA5 | Q91V01 | Lysophospholipid acyltransferase 5 | Lpcat3 | miRNA target (1/4) + Figure 1d | NS | — | — | — | NS | 1.09 | 0.13 | 0.21 | NS | — | NS | — | — | — |
| ADA10 | O35598 | Disintegrin metalloproteinase domain-containing protein 10 | Adam10 | miRNA target (3/4) | NS | (▴) | — | — | NS | 1.03 | 0.59 | 0.73 | NS | NS | NS | 1.04 | 0.696 | 0.7443 |
| ANFY1 | Q810B6 | Ankyrin repeat and FYVE domain-containing protein 1 | Ankfy1 | miRNA target (1/4) | NS | — | — | — | NS | 1.02 | 0.85 | 0.91 | NS | NS | NS | 1.22 | 0.05 | 0.07 |
| Discovery | ||||||||||||||||||
| PP2BC | P48455 | Serine/threonine-protein phosphatase 2B catalytic γ isoform | Ppp3cc | Figure 1d | NS | ▴ | ▴ | ▴ | ▴ | 1.06 | 1.1E-02 | 3.1E-02 | NS | NS | ▴ | 1.21 | 4.7E-10 | 4.8E-09 |
| PP2BB | P48453 | Serine/threonine-protein phosphatase 2B catalytic β isoform | Ppp3cb | NS | NS | NS | NS | ▴ | 1.16 | 5.8E-04 | 2.4E-03 | NS | NS | ▴ | 1.16 | 8.9E-03 | 1.6E-02 | |
| NFL | P08551 | Neurofilament light polypeptide (NF-L) | Nefl | Figure 1d | NS | ▴ | - | ▴ | ▴ | 1.09 | 1.8E-03 | 6.3E-03 | NS | NS | ▴ | 1.15 | 1.6E-04 | 4.9E-04 |
| AINX | P46660 | Alpha-internexin (Alpha-Inx) | Ina | Figure 1d | NS | ▴ | — | ▴ | NS | 0.96 | 0.31 | 0.42 | NS | NS | ▴ | 1.21 | 3.0E-08 | 2.3E-07 |
| NRDC | Q8BHG1 | Nardilysin (EC 3.4.24.61) | Nrd1 | Figure 1d | NS | — | ▾ | ▾ | NS | 1.02 | 0.60 | 0.73 | NS | NS | NS | 0.99 | 0.89 | 0.90 |
| VGLU1 | Q3TXX4 | Vesicular glutamate transporter 1 (VGluT1) | Slc17a7 | Transcriptomics5 | ⇑ | NS | — | — | ▴ | 1.16 | 1.6E-06 | 1.4E-05 | ⇑ | NS | ▴ | 1.19 | 1.5E-04 | 4.8E-04 |
| Implicated pathways | ||||||||||||||||||
| mTOR–autism spectrum disorders and mental retardation | ||||||||||||||||||
| MTOR | Q9JLN9 | Serine/threonine-protein kinase mTOR | Mtor | NS | — | — | — | ▴ | 1.28 | 4.8E-04 | 2.1E-03 | NS | NS | NS | 1.10 | 0.30 | 0.34 | |
| MK03 | Q63844 | Mitogen-activated protein kinase 3 (ERK-1) | Mapk3 | NS | ▴ | — | — | ▴ | 1.16 | 2.3E-05 | 1.5E-04 | NS | NS | ▴ | 1.23 | 3.7E-05 | 1.3E-04 | |
| MK01 | P63085 | Mitogen-activated protein kinase 1 (ERK-2) | Mapk1 | NS | ▴ | — | — | ▴ | 1.11 | 5.9E-05 | 3.0E-04 | NS | NS | ▴ | 1.07 | 6.3E-03 | 1.2E-02 | |
| PEA15 | Q62048 | Astrocytic phosphoprotein PEA-15 | Pea15 | NS | ▴ | — | — | ▴ | 1.15 | 5.0E-05 | 2.8E-04 | NS | — | ▾ | 0.91 | 2.8E-02 | 4.4E-02 | |
| KPCG | P63318 | Protein kinase C gamma type | Prkcg | ⇑ | (▴) | NS | NS | ▴ | 1.11 | 1.2E-03 | 4.6E-03 | NS | NS | ▴ | 1.21 | 6.2E-07 | 2.9E-06 | |
| Glutamatergic signalling—schizophrenia and affective disorders | ||||||||||||||||||
| NMDZ1 | P35438 | Glutamate receptor ionotropic, NMDA 1 (NMD-R1) | Grin1 | Hippocampus network5 | NS | — | — | — | ▴ | 1.15 | 0.015 | 3.8E-02 | ⇑ | NS | ▴ | 1.86 | 1.1E-12 | 2.3E-11 |
| GRIA1 | P23818 | Glutamate receptor 1 (GluR-1) | Gria1 | Hippocampus network5 | ⇑ | NS | — | — | NS | 1.08 | 0.18 | 0.26 | ⇑ | NS | ▴ | 1.43 | 2.7E-06 | 1.0E-05 |
| GRIA2 | P23819 | Glutamate receptor 2 (GluR-2) | Gria2 | NS | — | NS | (▴) | ▴ | 1.12 | 4E-04 | 2E-03 | NS | ▾ | ▴ | 1.25 | 1.9E-12 | 2.9E-11 | |
| GRIA3 | Q9Z2W9 | Glutamate receptor 3 (GluR-3) | Gria3 | Hippocampus network5 | NS | — | NS | — | NS | 1.03 | 0.64 | 0.76 | ⇑ | — | ▴ | 1.30 | 1.1E-03 | 2.6E-03 |
| KCC2A | P11798 | Calcium/calmodulin-dependent protein kinase type II α | Camk2a | Hippocampus network5 | ⇑ | NS | ▴ | — | NS | 1.05 | 0.20 | 0.28 | ⇑ | NS | ▴ | 1.27 | 1.6E-07 | 1.1E-06 |
| KCC2G | Q923T9 | Calcium/calmodulin-dependent protein kinase type II γ | Camk2g | NS | NS | NS | NS | NS | 1.05 | 0.11 | 0.20 | NS | NS | ▴ | 1.25 | 1.7E-04 | 4.9E-04 | |
| SYT1 | P46096 | Synaptotagmin-1 | Syt1 | Hippocampus network5 | NS | NS | ▾ | ▴ | NS | 1.05 | 0.07 | 0.13 | ⇑ | NS | NS | 1.08 | 0.05 | 0.08 |
| DLG4 | Q62108 | Disks large homolog 4 | Dlg4 | Hippocampus network5 | ⇑ | — | — | NS | NS | 1.00 | 0.81 | 0.88 | ⇑ | NS | ▴ | 1.17 | 7.6E-05 | 2.6E-04 |
| NCDN | Q9Z0E0 | Neurochondrin (Norbin) | Ncdn | ⇑ | NS | NS | ▴ | (▴) | 1.09 | 0.05 | 0.10 | NS | NS | ▴ | 1.27 | 3.0E-03 | 6.2E-03 | |
| Housekeeping | ||||||||||||||||||
| RL8 | P62918 | 60S ribosomal protein L8 | Rpl8 | ⇓ | — | — | — | NS | 1.05 | 0.35 | 0.46 | NS | NS | — | — | — | — | |
| MAP2 | O08663 | Methionine aminopeptidase 2 | Metap2 | NS | NS | NS | NS | NS | 1.04 | 0.21 | 0.29 | NS | NS | NS | 1.06 | 0.04 | 0.06 | |
| RS3A | P97351 | 40S ribosomal protein S3a | Rps3a | NS | — | — | — | NS | 1.04 | 0.11 | 0.20 | NS | NS | (▴) | 1.12 | 0.04 | 0.06 | |
Abbreviations: HFC, hippocampus; NS, not significant. Significantly (P*<0.05) downregulated and upregulated in proteomic profiling (▾▴) or transcriptomic profiling5, 8 (⇑⇓), in brackets if only P<0.05; PFC, prefrontal cortex; —, not detected.
Findings are compared with label-free LC-MSE proteomic discovery profiling and transcriptomic profiling results. Italicized cells indicates consistency across the studies. Column ‘Label' indicates implication of protein (for example, predicted miRNA target by Xof4 bioinformatic prediction tools). P-values were determined using SRMstats and corrected for multiple hypothesis testing (P*).18