Study Report

Reference

Citation	Martins-de-Souza D, 2012 PubMed
Full Info	Martins-de-Souza D, Guest PC, Vanattou-Saifoudine N, Rahmoune H, Bahn S. Phosphoproteomic differences in major depressive disorder postmortem brains indicate effects on synaptic function. Eur Arch Psychiatry Clin Neurosci 2012.

Study

Hypothesis or Background	There is still a lack in the molecular comprehension of major depressive disorder (MDD) although this condition affects approximately 10% of the world population. Protein phosphorylation is a posttranslational modification that regulates approximately one-third of the human proteins involved in a range of cellular and biological processes such as cellular signaling. Whereas phosphoproteome studies have been carried out extensively in cancer research, few such investigations have been carried out in studies of psychiatric disorders.
Sample Information	24 MDD patients and 12 control donors
Method Detail	Here, we present a comparative phosphoproteome analysis of postmortem dorsolateral prefrontal cortex tissues from 24 MDD patients and 12 control donors. Tissue extracts were analyzed using liquid chromatography mass spectrometry in a data-independent manner (LC-MS(E)).
Method Keywords	spectrophotometric analysis
Result	Our analyses resulted in the identification of 5,195 phosphopeptides, corresponding to 802 non-redundant proteins. Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls, being 20 differentially phosphorylated in at least 2 peptides.
Conclusions	The majority of these phosphorylated proteins were associated with synaptic transmission and cellular architecture not only pointing out potential biomarker candidates but mainly shedding light to the comprehension of MDD pathobiology.

Relationships reported by Martins-de-Souza D, 2012

Component A Approved Name (Name in Paper)	Component A Type	Component B Approved Name (Name in Paper)	Component B Type	Relationship Description	Result Category (Positive/Negative))
MDD	syndrome	Putative tubulin-like protein alpha-4B (Putative tubulin beta-4q chain)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Tubulin beta-1 chain (Tubulin beta-1 chain)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Calcium/calmodulin-dependent protein kinase type II subunit alpha (Calcium calm dep prot kinase type 2 alpha chain)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Vimentin (Vimentin)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Syntaxin-1B (Syntaxin 1B)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Spectrin beta chain, non-erythrocytic 2 (Spectrin beta chain, brain 2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Putative tubulin-like protein alpha-4B (Putative tubulin-like protein alpha-4B)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Microtubule-associated protein tau (full microtubule associated protein tau)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Dihydropyrimidinase-related protein 2 (Dihydropyrimidinase-related protein 2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Dihydropyrimidinase-related protein 1 (Dihydropyrimidinase-related protein 1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Guanine nucleotide-binding protein G(olf) subunit alpha (Guanine nucleotide binding protein G olf subunit alpha)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Peptidyl-prolyl cis-trans isomerase FKBP2 (FK506 binding protein 2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Dynamin-1 (Dynamin-1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Contactin-associated protein 1 (contactin associated protein 1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Dynamin-3 (Dynamin-3)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Dynamin-2 (Dynamin-2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	ATP-dependent RNA helicase DDX1 (ATP dependent RNA helicase DDX1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	DNA-binding protein SATB2 (DNA-binding protein SATB2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Myelin basic protein (Myelin basic protein)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Acetyl-coenzyme A synthetase 2-like, mitochondrial (Acetyl-coenzyme A synthetase 2-like, mitochondrial)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Guanine nucleotide-binding protein G(o) subunit alpha (Guanine nucleotide binding protein G o subunit alpha)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Receptor-type tyrosine-protein phosphatase delta (receptor-type tyrosine-protein phosphatase delta)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Receptor-type tyrosine-protein phosphatase zeta (receptor-type tyrosine-protein phosphatase zeta)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Ras-related protein Rab-39B (Ras related protein Rab 39B)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Putative Rab-43-like protein ENSP00000330714 (Putative Rab 43 like protein ENSP00000330714)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Synaptic vesicle glycoprotein 2A (synaptic vesicle glycoprotein 2A)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	ER membrane protein complex subunit 2 (Tetratricopeptide repeat protein 35)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Testis-specific Y-encoded-like protein 1 (Testis specific Y encoded like protein 1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Cytoplasmic FMR1-interacting protein 1 (cytoplasmic FMR1 interacting protein 1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Eukaryotic translation initiation factor 3 subunit M (eukaryotic translation initiation factor 3 subunit M)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	CST complex subunit STN1 (Oligonuc/oligosac-binding fold containing protein 1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Neurofilament medium polypeptide (Neurofilament medium polypeptide)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Neurofilament light polypeptide (Neurofilament light polypeptide)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Spectrin beta chain, non-erythrocytic 1 (Spectrin beta chain, brain 1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Spectrin alpha chain, non-erythrocytic 1 (Spectrin alpha chain, brain)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Microtubule-associated protein 1A (microtubule-associated protein 1A)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Mitochondrial inner membrane protein (Mitochondrial inner membrane protein)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Microtubule-associated protein 2 (microtubule-associated protein 2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Microtubule-associated protein 1B (microtubule-associated protein 1B)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Desmocollin-1 (Desmocollin 1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Desmoplakin (Desmoplakin)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Fascin (fasin)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Band 4.1-like protein 3 (Band 4 1 like protein 3)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Clathrin heavy chain 2 (Clathrin heavy chain 2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Clathrin heavy chain 1 (Clathrin heavy chain 1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Cytoplasmic dynein 1 intermediate chain 1 (cytoplasmic dynein 1 intermediate chain 1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Contactin-1 (Contactin1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Alpha-actinin-4 (Alpha-actinin-4)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Beta-adducin (Beta-adducin)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Alpha-internexin (Alpha-internexin)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Cadherin-13 (Cadherin-13)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Stress-70 protein, mitochondrial (Stress-70 protein, mitochondrial)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	60 kDa heat shock protein, mitochondrial (60 kDa heat shock protein, mitochondrial)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Actin, aortic smooth muscle (Actin, aortic smooth muscle)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Beta-actin-like protein 2 (Beta-actin-like protein 2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Putative heat shock protein HSP 90-beta-3 (putative heat shock protein HSP 90-beta-3)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Heat shock 70 kDa protein 12A (heat shock 70 kDa protein 12A)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Heat shock 70 kDa protein 1-like (heat shock 70 kDa protein 1L)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Heat shock-related 70 kDa protein 2 (heat shock-related 70 kDa protein 2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Cytosolic non-specific dipeptidase (cytosolic non-specific dipeptidase)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Alpha-crystallin B chain (alpha-crystallin B chain)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Putative heat shock protein HSP 90-alpha A2 (putative heat shock protein HSP 90-alpha A2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Heat shock protein HSP 90-beta (Heat shock protein HSP 90- Beta)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	ADP/ATP translocase 2 (ADP/ATP translocase 2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Peroxiredoxin-2 (Peroxiredoxin-2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Phosphoglycerate kinase 1 (Phosohoglycerate kinase 1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Protein disulfide-isomerase A4 (Protein disulfide-isomerase A4)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Vesicle-fusing ATPase (N-ethylmaleimide-sensitive fusion protein)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	L-lactate dehydrogenase A chain (L-lactate dehydrogenase A chain)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Hexokinase-2 (hexokinase-2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Beta-enolase (beta-endase)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Gamma-enolase (gamma-endase)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	2',3'-cyclic-nucleotide 3'-phosphodiesterase (2 3 cyclic nucleotide 3 phosphodiesterase)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	ATP synthase subunit alpha, mitochondrial (ATP synthase subunit alpha)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Potassium-transporting ATPase alpha chain 1 (Potassium-transporting ATPase alpha chain 1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Aconitate hydratase, mitochondrial (aconitate hydratase mitochondrial)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Synapsin-1 (synapsin-1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	4F2 cell-surface antigen heavy chain (4F2 cell surface antigen heavy chain)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Calcium-binding mitochondrial carrier protein Aralar1 (calcium binding mitochondrial carrier protein aralar1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Rabphilin-3A (Rabphilin 3A)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Excitatory amino acid transporter 4 (Excitatory amino acid transporter 4)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Calcium-dependent secretion activator 1 (Calcium dependent secretion activator 1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Rab GDP dissociation inhibitor beta (Rab GDP dissociation inhabitor beta)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Plasma membrane calcium-transporting ATPase 4 (Plasma membrane calcium-transporting ATPase 4)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	V-type proton ATPase subunit G 2 (V typeproton ATPase subunit G2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Sodium/potassium-transporting ATPase subunit alpha-4 (Na/K-transporting ATPase subunit alpha-4)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Plasma membrane calcium-transporting ATPase 3 (Plasma membrane calcium-transporting ATPase)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Sodium/potassium-transporting ATPase subunit alpha-1 (Na/K-transporting ATPase subunit alpha 1)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	Sodium/potassium-transporting ATPase subunit alpha-3 (Na/K-transporting subunit alpha-3)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive
MDD	syndrome	AP-2 complex subunit alpha-2 (AP2 complex subunit alpha 2)	protein	Ninety of these proteins showed differential levels of phosphorylation in tissues from MDD subjects compared to controls	Positive