Table 3.
Summary of PL studies that have been coupled to MS-based proteomic analyses to identify and characterize neurobiology-related PPIs
| S. no.: | Tissue/cells | PL approach | MS method | Target protein | Clinical condition/classification | Reference |
|---|---|---|---|---|---|---|
| Cell type specific/subcellular | ||||||
| 1 | Mice VM dopamine neurons | Ex vivo/APEX2 | Data-independent acquisition | APEX2-NES | Midbrain subcellular proteomics, cell type specific | (88) |
| 2 | Mouse dorsal striatum SPN subtypes | APEX2 ex vivo | TMT | Cre-dependent expression of APEX2 in nucleus (H2B fusion), cytosol (NES), or plasma membrane (membrane anchor LCK sequence) | Striatal subcellular, D1 or D2 SPNs, cell type specific | (89) |
| 3 | Mouse cortex, hippocampus, striatum/thalamus, pons/medulla, and cerebellum | TurboID | Data-dependent acquisition (DDA) with high-field asymmetric waveform ion mobility spectrometry (FAIMS Pro) | Viral or Cre-dependent expression of TurboID in Ca2+/calmodulin-activated protein kinase 2A–expressing neurons | Cell type–specific proteomics | (90) |
| Synaptic proteins (presynaptic/postsynaptic and synaptic cleft) | ||||||
| 4 | C. elegans | In vivo/TurboID | DDA | ELKS/RAB6-interacting/CAST family member 2 | Presynaptic proteins | (92) |
| 5 | Rat primary cortical neurons | In vitro/HRP | Isobaric tags for relative and absolute quantification (iTRAQ) | Glutamatergic excitatory synaptic proteins (Lrrtm1 and Lrrtm2) and GABAergic inhibitory synaptic proteins (Slitrk3 and Nlgn2) | Excitatory and inhibitory synaptic cleft proteins | (54) |
| 6 | Rat primary cortical neurons | In vitro/HRP | DDA | Synaptic cell adhesion protein 1/SynCAM1-HRP | Synaptic cleft | (93) |
| 7 | Mouse cortex | iBioID | DDA | PSD protein 95 (excitatory synapses) or gephyrin (inhibitory synapses) | Inhibitory and excitatory PSD, synapses | (94) |
| 8 | CD1 juvenile mouse brain (P21) | Split-TurboID | DDA | Neuronal-specific promoter (hsyn1) and astrocyte-specific promoter (GfaABC1D) fused to N-terminal and C-terminal TurboID fragments | Astrocyte–neuron signaling, cell–cell interaction | (96) |
| Axonal growth cone/dendritic spine proteins | ||||||
| 9 | Rat primary hippocampal neurons | In vitro/BioID | DDA | NF186, nuclear distribution element-like 1 (NDEL1), tripartite motif–containing protein 46 (Trim46) | Axonal initial segment | (97) |
| 10 | Mouse cortical cells (in vivo) | BioID-2 | DDA | Synaptopodin | Dendritic spines, spine apparatus, synaptic proteins | (100) |
| Lysosomal proteins and endolysosomal pathway | ||||||
| 11 | human induced pluripotent stem cell (iPSC)–derived neurons | In vitro/APEX | DDA | LAMP1-APEX | Neuronal lysosomal proteins | (101) |
| 12 | HEK293 cells | BioID | DDA | TMEM16K | Endolysosomal pathway, spinocerebellar ataxia, endosomal retrograde transport | (102) |
| Dopamine and glutamate transporter proteins | ||||||
| 13 | HT22 neuroblastoma cell lines | In vitro/BioID | DDA | DAT | Striatal dopamine transport, neurotransmission, and signal transduction | (103) |
| 14 | H22 hippocampal cell line | In vitro/BioID | DDA | DAT and glutamate transporter (GLT-1) | Neurotransmission and signal transduction | (104) |
| Signaling receptors and kinases | ||||||
| 15 | SH-SY5Y human neuroblastoma cell line, rat cortical neurons | In vitro/photoTurboID | DDA | Mitochondrial–ER lumen–localizing sequence | PTMs, phosphorylation, and signaling | (107) |
| 16 | Drosophila larval brain | In vivo/TurboID and miniTurbo | TMT | Alk | Kinase signaling | (108) |
| 17 | HEK293 cells | BioID | DDA | Ephrin-B2 (EphB2) | Cell-surface receptor signaling, neurodevelopment | (109) |
| NDDs/neurodifferentiation | ||||||
| 18 | O9-1 mouse cranial neural crest cell line | In vitro/BioID | DDA | Twist Family BHLH Transcription Factor 1 (TWIST1) | Neurodevelopment/differentiation | (111) |
| 19 | AD293 cell (HEK cells) | BioID | DDA | TLK2 | Mental retardation autosomal dominant 57, neurodevelopment/differentiation | (113) |
| 20 | Mouse retinal progenitor cells | In vitro/BioID | DDA | Zinc finger transcription factor (Casz1) | Neurodevelopment/differentiation | (114) |
| 21 | Mice primary cortical neuronal cells | In vitro/BioID | DDA | PARP6 | Dendrite morphogenesis, neurodevelopment | (115) |
| 22 | Mouse primary cortical neuronal cells | In vitro/BioID | DDA | TRIM9 and TRIM67 | Neuronal differentiation | (116) |
| 23 | Drosophila olfactory PNs | In situ/HRP | TMT | Rat CD-2 | Neurodevelopment, neurodifferentiation | (117) |
| 24 | Mouse hippocampus and cortex | iBioID | DDA | Wave-related protein (WRP)-FBAR domain in dendritic filopodia | Synaptogenesis, excitatory synapses, and neurodevelopment | (118) |
| 25 | Rat primary hippocampal neurons | In vitro/BioID2 | DDA | MeCP2 | NDDs, Rett syndrome | (119) |
| Neurodegenerative disorders | ||||||
| 26 | Rat primary cortical neurons | In vitro/APEX-2 | iTRAQ | α-synuclein | PD synucleinopathies | (121) |
| 27 | Human neuroblastoma SH-SY5Y cells | In vitro/BioID | DDA | α-Synuclein WT or A53T | PD synucleinopathies | (122) |
| 28 | Human postmortem tissue—substantia nigra, striatum, cortex | In situ/BAR | DDA | Synuclein 1 and phosphorylated synuclein (PSER129) | PD synucleinopathies | (123) |
| 29 | Human iPSC–derived glutamatergic neurons | In vitro/APEX-2 | DDA | N or C terminus truncated Tau | Taupathies, neurodegenerative disorders, AD, and FTD | (126) |
| 30 | HT-22 cells (immortalized rat hippocampal cell line) | In vitro/BioID | DDA | Beta-site amyloid precursor protein cleaving enzyme 1 (BACE1) | Neurodegenerative disorder and AD | (128) |
| 31 | Neuro-2a (N2a) cells | In vitro/BirA∗ biotin ligase | DDA | Ataxin-1 protein | Neurodegenerative disease and nuclear transport | (129) |
| 32 | Mouse N2a neuroblastoma cells | In vitro/BioID | DDA | TDP-43 | ALS/FTD, neurodegenerative disorders, cytonucleoplasmic transport | (130) |
| 33 | HEK293T | BioID | DDA | Cyclin F | ALS/FTD, cytonucleoplasmic transport | (131) |
| 34 | HEK293T cells (American Type Culture Collection CRL-11268) | BioID | diaPASEF | Dipeptide repeat (DPR) proteins detected in the brains of FTD/ALS patients with C9orf72 repeat expansions (c9FTD/ALS) | ALS/FTD, cytonucleoplasmic transport | (132) |