Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis
Abstract
:1. Introduction
2. Results and Discussion
2.1. OB Proteome-Wide Analysis in Human ALS
2.2. Functional Analysis for the Differential Ob Proteome Detected in ALS
2.3. Imbalance in Survival Pathways Across the Olfactory Bulb-Tract Axis in ALS
3. Materials and Methods
3.1. Materials
3.2. Human Samples
3.3. Sample Preparation for Proteomic Analysis
3.4. Label Free LC-MS/MS
3.5. Protein Identification and Quantification
3.6. Bioinformatics
3.7. Western-Blotting
4. Conclusions
Supplementary Materials
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
Abbreviations
ALS | Amyotrophic lateral sclerosis |
CAMK II | Calmodulin-dependent protein kinase II |
ERK | Extracellular signal-regulated kinase |
FDR | False discovery rate |
MEK | Mitogen-activated protein kinase kinase |
OB/OT | Olfactory bulb/olfactory tract |
OMP | Olfactory marker protein |
p38 MAPK | p38 mitogen-activated protein kinase |
PKA | Protein kinase A |
PKC | Protein kinase C |
PMI | Post-mortem interval |
SAPK/JNK | (stress-activated protein kinase/Jun-amino terminal kinase) |
SEK1 | Mitogen-activated protein kinase Kinase 4 |
TDP43 | TAR DNA-binding protein 43 |
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Protein ID | Protein Name | Gene | p Value | FC | Activity/Pathway |
---|---|---|---|---|---|
P80723 | Brain acid soluble protein 1 | BASP1 | 0.00 | 0.20 | transcription corepressor activity |
P08123 | Collagen alpha-2(I) chain | COL1A2 | 0.00 | 0.21 | Integrin Pathway & Collagen trimerization |
Q96PE5 | Opalin | OPALIN | 0.01 | 0.35 | oligodendrocyte terminal differentiation |
Q7Z6Z7 | E3 ubiquitin-protein ligase HUWE1 | HUWE1 | 0.01 | 0.38 | proteasomal degradation |
O15230 | Laminin subunit alpha-5 | LAMA5 | 0.04 | 0.39 | Integrin Pathway & signaling by GPCR |
Q09666 | Neuroblast differentiation-associated protein AHNAK | AHNAK | 0.02 | 0.44 | Phospholipase-C Pathway |
F5H7S3 | Tropomyosin alpha-1 chain | TPM1 | 0.03 | 0.47 | cytoskeletal protein binding |
O43852 | Calumenin | CALU | 0.00 | 0.48 | calcium ion binding |
Q5T4S7 | E3 ubiquitin-protein ligase UBR4 | UBR4 | 0.03 | 0.48 | ubiquitin-protein transferase activity |
P13521 | Secretogranin-2 | SCG2 | 0.00 | 0.50 | chemoattractant activity |
Q02818 | Nucleobindin-1 | NUCB1 | 0.00 | 0.52 | Golgi calcium homeostasis |
P21333 | Filamin-A | FLNA | 0.00 | 0.57 | crosslink actin filaments |
P39019 | 40S ribosomal protein S19 | RPS19 | 0.03 | 0.58 | pre-rRNA processing |
Q6IQ22 | Ras-related protein Rab-12 | RAB12 | 0.05 | 0.58 | Vesicle trafficking |
O75643 | U5 small nuclear ribonucleoprotein 200 kDa helicase | SNRNP200 | 0.02 | 0.61 | mRNA splicing |
P11277 | Spectrin beta chain, erythrocytic | SPTB | 0.03 | 0.62 | actin filament binding |
Q93008 | Probable ubiquitin carboxyl-terminal hydrolase FAF-X | USP9X | 0.01 | 0.64 | deubiquitinase, protein turnover |
Q9NXU5 | ADP-ribosylation factor-like protein 15 | ARL15 | 0.04 | 0.64 | GTP binding |
Q15149 | Plectin | PLEC | 0.05 | 0.66 | Cytoskeleton remodeling Neurofilaments |
F5GWT4 | Serine/threonine-protein kinase WNK1 | WNK1 | 0.04 | 0.67 | regulation of electrolyte homeostasis |
Q9H444 | Charged multivesicular body protein 4b | CHMP4B | 0.00 | 0.67 | sorting of endocytosed cell-surface receptors |
Q08AD1 | Calmodulin-regulated spectrin-associated protein 2 | CAMSAP2 | 0.03 | 0.68 | regulator of neuronal polarity |
Q02952 | A-kinase anchor protein 12 | AKAP12 | 0.00 | 0.70 | subcellular compartmentation of PKA/PKC |
P21980 | Protein-glutamine gamma-glutamyltransferase 2 | TGM2 | 0.03 | 0.71 | cross-linking and conjugation of polyamines |
P11137 | Microtubule-associated protein 2 | MAP2 | 0.04 | 0.71 | stabilization of microtubules |
Q96RT1 | Protein LAP2 | ERBB2IP | 0.00 | 0.72 | Inhibits proinflammatory cytokine secretion |
Q01082 | Spectrin beta chain, non-erythrocytic 1 | SPTBN1 | 0.02 | 0.72 | movement of the cytoskeleton |
P05387 | 60S acidic ribosomal protein P2 | RPLP2 | 0.03 | 0.73 | protein synthesis |
O75746 | Calcium-binding mitochondrial carrier protein Aralar1 | SLC25A12 | 0.04 | 0.74 | exchange of Asp for Glu in the mitochondria |
P27338 | Amine oxidase [flavin-containing] B | MAOB | 0.00 | 0.75 | metabolism of neuroactive and vasoactive amines |
Q00325 | Phosphate carrier protein, mitochondrial | SLC25A3 | 0.04 | 0.75 | regulation of mitochondrial permeability |
P19022 | Cadherin-2 | CDH2 | 0.00 | 0.75 | cell-cell adhesion |
P09497 | Clathrin light chain B | CLTB | 0.02 | 0.77 | vesicle biogenesis |
P07093 | Glia-derived nexin | SERPINE2 | 0.01 | 1.33 | endopeptidase inhibitor activity |
Q08623 | Pseudouridine-5-phosphatase | HDHD1 | 0.04 | 1.35 | pyrimidine nucleoside salvage |
Q7Z2Z2 | Elongation factor Tu GTP-binding domain-containing protein 1 | EFTUD1 | 0.03 | 1.41 | translational activation of ribosomes |
P00491 | Purine nucleoside phosphorylase | PNP | 0.01 | 1.43 | nucleoside binding |
P49356 | Protein farnesyltransferase subunit beta | FNTB | 0.01 | 1.43 | farnesyltransferase activity |
O60825 | 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 2 | PFKFB2 | 0.04 | 1.44 | Synthesis/degradation of fructose 2,6-bisP |
Q9H3P7 | Golgi resident protein GCP60 | ACBD3 | 0.02 | 1.44 | maintenance of Golgi structure |
P50336 | Protoporphyrinogen oxidase | PPOX | 0.05 | 1.45 | heme biosynthesis |
Q9GZV7 | Hyaluronan and proteoglycan link protein 2 | HAPLN2 | 0.05 | 1.45 | establishment of blood-nerve barrier |
Q96P70 | Importin-9 | IPO9 | 0.01 | 1.46 | nuclear protein import |
P02790 | Hemopexin | HPX | 0.04 | 1.53 | heme transport |
Q9BW30 | Tubulin polymerization-promoting protein family member 3 | TPPP3 | 0.01 | 1.54 | Regulator of microtubule dynamics |
Q9UHQ9 | NADH-cytochrome b5 reductase 1 | CYB5R1 | 0.01 | 1.62 | desaturation/elongation of fatty acids |
O75608 | Acyl-protein thioesterase 1 | LYPLA1 | 0.03 | 1.64 | phospholipase activity |
Q5SSJ5 | Heterochromatin protein 1-binding protein 3 | HP1BP3 | 0.04 | 1.66 | heterochromatin organization |
Q13049 | E3 ubiquitin-protein ligase TRIM32 | TRIM32 | 0.02 | 1.69 | ubiquitin-protein transferase activity |
O95081 | Arf-GAP domain and FG repeat-containing protein 2 | AGFG2 | 0.01 | 1.70 | GTPase activator activity |
Q8IWZ6 | Bardet-Biedl syndrome 7 protein | BBS7 | 0.01 | 1.70 | cilium assembly |
F5GZH3 | Pleckstrin homology domain-containing family B member 1 | PLEKHB1 | 0.03 | 1.73 | cell differentiation |
A6NGJ0 | Dynein light chain Tctex-type 3 | DYNLT3 | 0.04 | 1.76 | intracellular retrograde motility of vesicles |
Q8IZ83 | Aldehyde dehydrogenase family 16 member A1 | ALDH16A1 | 0.04 | 1.82 | oxidoreductase activity |
Q9NQW6 | Actin-binding protein anillin | ANLN | 0.04 | 1.91 | actomyosin contractile ring assembly |
P05230 | Fibroblast growth factor 1 | FGF1 | 0.04 | 1.96 | Integrin binding |
O43924 | GMP-Phosphodiesterase delta | PDE6D | 0.04 | 1.97 | ciliary targeting of farnesylated proteins |
P42574 | Caspase-3;Caspase-3 subunit p17;Caspase-3 subunit p12 | CASP3 | 0.04 | 1.99 | apoptosis execution |
Q9HCB6 | Spondin-1 | SPON1 | 0.02 | 2.01 | attachment of spinal cord & sensory neuron cells |
Q6UWE0 | E3 ubiquitin-protein ligase LRSAM1 | LRSAM1 | 0.01 | 2.12 | ubiquitin-protein transferase activity |
P12271 | Retinaldehyde-binding protein 1 | RLBP1 | 0.04 | 2.22 | retinoid metabolism |
Q8N7J2 | APC membrane recruitment protein 2 | AMER2 | 0.04 | 2.23 | Wnt signaling pathway |
O75695 | Protein XRP2 | RP2 | 0.01 | 2.40 | post-Golgi vesicle-mediated transport |
H3BLV0 | Complement decay-accelerating factor | CD55 | 0.01 | 2.45 | regulation of the complement cascade |
Q9Y2W1 | Thyroid hormone receptor-associated protein 3 | THRAP3 | 0.02 | 2.49 | regulation of mRNA splicing & transcription |
P47874 | Olfactory marker protein | OMP | 0.04 | 2.84 | modulator of the olfactory signal-transduction |
P00738 | Haptoglobin | HPR | 0.03 | 4.12 | antioxidant activity |
P41219 | Peripherin | PRPH | 0.05 | 4.46 | Class-III neuronal intermediate filament |
Groups | Age (years) | Onset | Sex | PMI | Neuropathological Diagnosis | AD Stages | OB Analysis | OT Analysis |
---|---|---|---|---|---|---|---|---|
Control | 65 | - | F | 3 h 45 m | Status cribosus | I/0 | Yes | No |
74 | - | M | 9 h 25 m | Lacunar infarction | III/A | Yes | No | |
45 | - | M | 18 h 30 m | Status cribosus | 0/0 | Yes | No | |
51 | - | F | 4 h | No lesions | 0/0 | Yes | Yes | |
67 | - | M | 5 h 50 m | Amyloid angiopathy | I/0 | Yes | Yes | |
59 | - | F | 5 h 30 m | Metastatic carcinoma | I/0 | Yes | Yes | |
60 | - | F | 12 h | Status cribosus | I/0 | Yes | Yes | |
75 | - | M | 5 h 30 m | Status cribosus | I/0 | Yes | Yes | |
ALS | 57 | Bulbar | M | 4 h | ALS | IIA | Yes | Yes |
75 | Bulbar | F | 4 h 5 m | ALS | IIA | Yes | Yes | |
79 | Spinal | F | 2 h 10 m | ALS | IIA | Yes | Yes | |
57 | Bulbar | F | 10 h | ALS | I/0 | Yes | Yes | |
50 | Spinal | M | 10 h 10 m | ALS | I/0 | Yes | Yes | |
75 | Bulbar | M | 3 h | ALS | II/B | Yes | Yes | |
71 | Spinal | M | 3 h 25 m | ALS | I/0 | Yes | Yes | |
68 | Bulbar | F | 16 h 30 m | ALS | I/0 | Yes | Yes | |
63 | Spinal | F | 18 h | ALS | I/0 | Yes | Yes | |
53 | Bulbar | F | 10 h | ALS | 0/0 | Yes | Yes | |
71 | Bulbar | F | 18 h | ALS | I/A | Yes | Yes | |
45 | Spinal | F | 4 h | ALS | 0/0 | Yes | Yes |
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Lachén-Montes, M.; Mendizuri, N.; Ausin, K.; Andrés-Benito, P.; Ferrer, I.; Fernández-Irigoyen, J.; Santamaría, E. Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis. Int. J. Mol. Sci. 2020, 21, 8311. https://doi.org/10.3390/ijms21218311
Lachén-Montes M, Mendizuri N, Ausin K, Andrés-Benito P, Ferrer I, Fernández-Irigoyen J, Santamaría E. Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis. International Journal of Molecular Sciences. 2020; 21(21):8311. https://doi.org/10.3390/ijms21218311
Chicago/Turabian StyleLachén-Montes, Mercedes, Naroa Mendizuri, Karina Ausin, Pol Andrés-Benito, Isidro Ferrer, Joaquín Fernández-Irigoyen, and Enrique Santamaría. 2020. "Amyotrophic Lateral Sclerosis Is Accompanied by Protein Derangements in the Olfactory Bulb-Tract Axis" International Journal of Molecular Sciences 21, no. 21: 8311. https://doi.org/10.3390/ijms21218311