Table 2.
Characterization of general astrocyte protein markers.
| Protein Marker | Full Name | Information |
|---|---|---|
| Structural and Membrane Proteins | ||
| AQP4 | aquaporin 4 | water homeostasis throughout the brain; localized in endfeet plasma membrane; highly expressed on Bergmann glia; not present at oligodendrocytes |
| BEST1 | bestrophin 1 | calcium-dependent transport of chloride ions, permeable for GABA and glutamate; mainly expressed in astrocytes; in mice distributed closer to the glutamatergic synapses than GABAergic synapses |
| CNN1 | calponin-1 | actin-related processes; enriched in astrocytes |
| Cx26 | connexin 26 | forms gap junction channels in glial network to maintain homeostasis of the CNS |
| Cx30 | connexin 30 | critical regulator of synaptic strength, controls location of astroglial processes and modulates glutamate transport; expressed only in mature astrocytes, mostly gray matter |
| Cx43 | connexin 43 | key player in brain development; abundantly expressed in adult CNS astrocyte endfeet |
| EAAT1 (GLAST) | excitatory amino acid transporter 1, glutamate aspartate transporter | glutamate uptake, co-compartmentalizes with mitochondria, supplying glutamate as a fuel for the brain; abundant in fine astrocyte processes, but also variably expressed by all cell types in the CNS |
| EAAT2 (GLT1) | excitatory amino acid transporter 2; glutamate transporter-1 | glutamate uptake, co-compartmentalizes with mitochondria, supplying glutamate as a fuel for the brain; abundant in fine astrocyte processes, but also variably expressed by all cell types in the CNS |
| ezrin | ezrin | protein anchoring the plasma membrane to cytoskeletal microfilaments; acts as stabilizer of filopodia (peripheral astrocyte processes) |
| FMN2 | formin-2 | actin-related processes; enriched in astrocytes |
| GAT-1 | sodium- and chloride-dependent GABA transporter 1 | GABA transporter; localized in distal astrocytic processes but in majority is expressed in neurons |
| GAT-3 | sodium- and chloride-dependent GABA transporter 3 | GABA transporter; localized mostly in processes adjacent to neuronal synapses; most numerous subtype in astrocytes |
| GFAP | glial fibrillary acidic protein | contributes to astroglial BBB mechanical support; expressed mainly by white matter astrocyte extensive branching and slightly their cell body; useful marker for studying complex astroglial morphology |
| KIR4. 1 | potassium inwardly-rectifying channels | controls cell hyperpolarization during resting potential, uptake of K+ from the synaptic cleft or its redistribution; in the normal adult CNS, KIR4.1 levels vary significantly in gray matter astroglia, downregulated in pathological conditions |
| NEBL | LIM zinc-binding domain-containing Nebulette | actin-related processes; enriched in astrocytes |
| nestin | nestin | marker of stem or progenitor cells |
| PDLIM7 | PDZ and LIM domain protein 7 | actin-related processes; enriched in astrocytes |
| radixin | radixin | connect the plasma membrane with cytoskeletal microfilaments; act as stabilizer of filopodia (peripheral astrocyte processes) |
| RSPH1 | radial spoke head 1 homolog | actin-related processes; astrocyte specific |
| synemin | synemin | intermediate filament; co-expressed by immature astrocytes along with GFAP, vimentin and nestin |
| SYNPO2 | synaptopodin-2 | actin-related processes; enriched in astrocytes |
| transitin | transitin | intermediate filament; expressed by radial glia during CNS development |
| vimentin | vimentin | role in differentiation and maturation of astrocytes; mostly expressed in some specialized glial cells such as Bergmann and radial glia or ependymal cells, white matter astrocytes |
| Transcription Factors and Intracellular Proteins | ||
| NF1A | nuclear factor 1 | maintains hippocampal astrocyte synapse-supporting functions; marker of glial lineages, including oligodendrocytes and astrocytes |
| NF1B | nuclear factor 2 | expressed in the adult brain olfactory bulb, hippocampus, cortex, and brainstem where they co-localize with ALDH1L1, also observed in neurons |
| NF1X | nuclear factor 3 | expressed in the adult brain olfactory bulb, hippocampus, cortex, and brainstem where they co-localize with ALDH1L1, also observed in neurons |
| NKX2-1 | NK homeobox gene-coded protein | regulates GFAP expression; controls astroglia production spatiotemporally in embryos |
| NKX3-1 | NK homeobox gene-coded protein | astrocytic region-specific transcription factor; exclusively expressed in astrocytes in olfactory bulb |
| NKX6-1 | NK homeobox gene-coded protein | astrocytic region-specific transcription factor; exclusively expressed in astrocytes in brainstem |
| SOX9 | SRY-related high mobility group (HMG) box gene 9 | nuclear marker; expressed almost exclusively in astrocytes; good astroglia marker in adult brain, outside the neurogenic zones, upregulated in reactive astrocytes |
| S100β | S100 calcium-binding protein β | cytosolic Ca++-binding protein, also secreted; labels cell bodies of small astrocytes with less extended branchinga, also expressed in neonatal oligodendrocytes, adult NG2 glia, ependymocytes and spinal, medullar, pontine and cerebellar neurons |
| Metabolic Markers | ||
| Glucose Related | ||
| ALDH1L1 | folate enzyme aldehyde dehydrogenase 1 family member L1 | converting NADP to NADPH; not homogenous expression, expressed in fibrous and protoplasmic astrocytes, and radial glia |
| FBP | fructose 1,6-bisphosphate | gluconeogenesis; production of glucose during starvation, astrocyte specific |
| G6PC | glucose 6-phosphatase | gluconeogenesis; production of glucose during starvation, astrocyte specific |
| GLUT1 | glucose transporter | glucose transport; less glycosylated isoform (45 kDa) found in astrocytes, more heavily glycolsylated isoform (55 kDa) is predominant in microvascular endothelium |
| GP | glycogen phosphorylase | glycogen utilization; astroglia-specific enzyme, degrades glycogen deposits in astroglia |
| GS | glycogen synthase | glycogen synthesis; selective to astrocytes, glycogen storage |
| LDH5 | lactate dehydrogenase | conversion of pyruvate to lactate; bidirectional enzyme biased towards the production of lactate, twofold enriched in astrocytes |
| MCT1 | monocarboxylate transporter 1 | responsible for pyruvate, lactate and ketone bodies transfer; expressed in astrocytes and oligodendrocytes lower affinity for lactate than the neuronal MCT2, expression is age-dependent |
| MCT4 | monocarboxylate transporter 4 | responsible for pyruvate, lactate and ketone bodies transfer; expressed only in astrocytes, much lower affinity for lactate than the neuronal MCT2, low affinity for ketone bodies |
| PC | pyruvate carboxylase | converts pyruvate into oxaloacetate in glycolysis; glial-specific anaplerotic enzyme, providing oxaloacetate for the TCA cycle |
| PDK4 | pyruvate dehydrogenase kinase 4 | phosphorylation-mediated inactivation of PDH; 30 times higher expression in astrocytes than in neurons; expressed also by microglial cells |
| PFKFB3 | 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-3 | converts fructose-6-phosphate to fructose-2,6-bisphosphate, regulates glycolysis and gluconeogenesis; enriched in astrocytes, a magnitude lower expression in neurons due to continuous degradation |
| PFK | phospho-fructokinase | higher expressed in astrocytes than in neurons |
| PKM2 | pyruvate kinase muscle isoform-2 | converts phosphoenolpyruvate to pyruvate, regulates glycolysis; enriched in astrocytes, expressed also by other glial cells |
| FAO Related | ||
| ABCA7 | ATP-binding cassette transporter 7 | cholesterol transporter |
| ABHD5 | 1-acylglycerol-3-phosphate O-acyltransferase 5 | membrane lipid metabolism and dynamics |
| APOE | apolipoprotein E | forms lipoprotein complex with cholesterol and is secreted through the ABCAs; expressed mainly in astrocytes but also found in microglia, found in neurons under pathological conditions |
| CTP1a | carnitine palmitoyltransferase 1a | citrate transporter protein, essential step for the mitochondrial uptake of long-chain fatty acids and beta-oxidation in mitochondrion; selective to astrocytes in outer membrane of mitochondrion, rate-limiting step of beta-oxidation |
| CTP2 | carnitine palmitoyltransferase 2 | citrate transporter protein, essential step for the mitochondrial uptake of long-chain fatty acids and beta-oxidation in mitochondrion; localized in mitochondrion inner membrane |
| DIO2 | type 2-deiodinase | removes iodide from L-thyroxine to produce 3, 3′5-triiodothyronine; thyroid hormone metabolism |
| ECL1 | enoyl-CoA delta isomerase 1 | oxidation of unsaturated fatty acids |
| ECL2 | enoyl-CoA delta isomerase 2 | oxidation of unsaturated fatty acids |
| FABP7 | fatty acid-binding protein 7 | high affinity reversible binding of saturated and unsaturated long-chain fatty acids; expression in neural stem cells throughout development, in adulthood decreases and becomes restricted to radial glia-like cells and astrocytes, abundant in astrocytes rich in cytoplasmic granules |
| GC-2 | mitochondrial glutamate carrier 2 | glutamate transport to the mitochondria; predominantly expressed in protoplasmic astrocyte cells but also in oligodendrocyte progenitor cells |
| GDH | glutamate dehydrogenase | oxidative deamination of glutamate to alpha-ketoglutarate |
| GK | glycerol kinase | membrane lipid metabolism and dynamics |
| GLDC | glycine decarboxylase | catabolism of glycogenic amino acids |
| GLP-1R | glucagon-like peptide-1 receptor | modulator of food intake and body weight |
| GLUL | glutamine synthetase | converts glutamate to glutamine; selectively expressed by astrocytes |
| GPAT3 | glycerol-3-phosphate acyltransferase | membrane lipid metabolism and dynamics |
| GPT2 | alanine aminotransferase 2 | catabolism of glycogenic amino acids |
| HADHA | hydroxyacyl-CoA dehydrogenase/3-ketoacyl-CoA thiolase/enoyl-CoA hydratase alpha | critical for the FAO regulation by T3; 95% of HADHA co-localize with GFAP in the brain |
| HIBADH | 3-hydroxyisobutyrate dehydrogenase | catabolism of glycogenic amino acids |
| HMGCR | 3-hydroxy-3-methylglutaryl-coenzyme A reductase | catalyzes the rate-limiting step in cholesterol synthesis |
| HMGCS2 | 3-hydroxy-3-methylglutaryl-CoA synthase 2 | converts acetyl-CoA to acetoacetate; rate-limiting enzyme in ketone bodies production, astrocyte specific |
| IDI1 | isopentenyl-diphosphate delta-isomerase 1 | membrane lipid metabolism and dynamics |
| LXR/RXR | liver X receptor/retinoid X receptor | activates production of cholesterol and mediates transcription of its transport proteins APOE and ABCA7 |
| PRODH | proline dehedrogenase 1 | catabolism of glycogenic amino acids |
| SCAP | SREBP cleavage-activating protein | mediates cholesterol synthesis; expressed in astrocytes and oligodendrocytes |
| SDSL | serine dehydratase-like | catabolism of glycogenic amino acids |
| SERHL | serine hydrolase-like | catabolism of glycogenic amino acids |
| SLCO1C1 | solute carrier organic anion transporter family member 1C1 transporter | transports L-thyroxine from the blood; thyroid hormone metabolism |
| SNAT3 | sodium-coupled neutral amino acid transporter 3 | glutamine transporter; suited for glutamine release |
| SNAT5 | sodium-coupled neutral amino acid transporter 5 | glutamine transporter; suited for glutamine release |