Astrocyte-neuron crosstalk regulates the expression and subcellular localization of carbohydrate metabolism enzymes
Abstract
Astrocytes releasing glucose- and/or glycogen-derived lactate and glutamine play a crucial role in shaping neuronal function and plasticity. Little is known, however, how metabolic functions of astrocytes, e.g., their ability to degrade glucosyl units, are affected by the presence of neurons. To address this issue we carried out experiments which demonstrated that co-culturing of rat hippocampal astrocytes with neurons significantly elevates the level of mRNA and protein for crucial enzymes of glycolysis (phosphofructokinase, aldolase, and pyruvate kinase), glycogen metabolism (glycogen synthase and glycogen phosphorylase), and glutamine synthetase in astrocytes. Simultaneously, the decrease of the capability of neurons to metabolize glucose and glutamine is observed. We provide evidence that neurons alter the expression of astrocytic enzymes by secretion of as yet unknown molecule(s) into the extracellular fluid. Moreover, our data demonstrate that almost all studied enzymes may localize in astrocytic nuclei and this localization is affected by the co-culturing with neurons which also reduces proliferative activity of astrocytes. Our results provide the first experimental evidence that the astrocyte-neuron crosstalk substantially affects the expression of basal metabolic enzymes in the both types of cells and influences their subcellular localization in astrocytes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In vitro glycolytic behavior can change with choice of culture media and astrocyte coculture.
“In vitro glycolytic behavior can change with choice of culture media (Sünwoldt et al., 2017) and astrocyte coculture (Mamczur et al., 2015), but gene expression data from acutely dissociated brain cells indicate that neurons are well equipped for glycolysis, with higher levels of mRNA expression than astrocytes for most glycolytic enzymes (Fig. 1, left).”
From Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism (2018) · cites this paper as Mamczur et al., 2015
Cites
Cox, J., & Mann, M. (2008) · Nature Biotechnology · doi:10.1038/nbt.1511 · Cited by 14,855 · see citing works
Universal sample preparation method for proteome analysis
Wiśniewski, J. R., Zougman, A., Nagaraj, N., & Mann, M. (2009) · Nature Methods · doi:10.1038/nmeth.1322 · Cited by 8,352 · see citing works
Self-citationPellerin, L., & Magistretti, P. J. (1994) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.91.22.10625 · Cited by 2,927 · see citing works
Astrocyte-Neuron Lactate Transport Is Required for Long-Term Memory Formation
Suzuki, A., Stern, S. A., Bozdagi, O., Huntley, G. W., Walker, R. H., Magistretti, P. J., & Alberini, C. M. (2011) · Cell · doi:10.1016/j.cell.2011.02.018 · Cited by 1,711 · see citing works
Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation
Yang, W., Xia, Y., Ji, H., Zheng, Y., Liang, J., Huang, W., Gao, X., Aldape, K., & Lu, Z. (2011) · Nature · doi:10.1038/nature10598 · Cited by 1,033 · see citing works
ERK1/2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect
Yang, W., Zheng, Y., Xia, Y., Ji, H., Chen, X., Guo, F., Lyssiotis, C. A., Aldape, K., Cantley, L. C., & Lu, Z. (2012) · Nature Cell Biology · doi:10.1038/ncb2629 · Cited by 910 · see citing works
Activity-dependent regulation of energy metabolism by astrocytes: an update
Pellerin, L., Bouzier‐Sore, A., Aubert, A., Serres, S., Merle, M., Costalat, R., & Magistretti, P. J. (2007) · Glia · doi:10.1002/glia.20528 · Cited by 805 · see citing works
Eng, L. F. (1985) · Journal of Neuroimmunology · doi:10.1016/s0165-5728(85)80063-1 · Cited by 737 · see citing works
Pellerin, L., & Magistretti, P. J. (2011) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2011.149 · Cited by 726 · see citing works
Pyruvate kinase type M2: A key regulator of the metabolic budget system in tumor cells
Mazurek, S. (2011) · The International Journal of Biochemistry & Cell Biology · doi:10.1016/j.biocel.2010.02.005 · Cited by 694 · see citing works
Schnitzer, J., Franke, W. W., & Schachner, M. (1981) · The Journal of Cell Biology · doi:10.1083/jcb.90.2.435 · Cited by 637 · see citing works
Astrocyte glycogen and brain energy metabolism
Brown, A. M., & Ransom, B. R. (2007) · Glia · doi:10.1002/glia.20557 · Cited by 626 · see citing works
Lactate Produced by Glycogenolysis in Astrocytes Regulates Memory Processing
Newman, L. A., Korol, D. L., & Gold, P. E. (2011) · PLoS ONE · doi:10.1371/journal.pone.0028427 · Cited by 473 · see citing works
D-valine as a selective agent for normal human and rodent epithelial cells in culture
Gilbert, S. F., & Migeon, B. R. (1975) · Cell · doi:10.1016/0092-8674(75)90086-0 · Cited by 389 · see citing works
Emerging roles of PKM2 in cell metabolism and cancer progression
Luo, W., & Semenza, G. L. (2012) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.06.010 · Cited by 380 · see citing works
The Ki-67 Protein: Fascinating Forms and an Unknown Function
Endl, E., & Gerdes, J. (2000) · Experimental Cell Research · doi:10.1006/excr.2000.4888 · Cited by 380 · see citing works
Lactate-mediated glia-neuronal signalling in the mammalian brain
Tang, F., Lane, S., KORSAK, A. S., Paton, J. F. R., Gourine, A. V., Kasparov, S., & Teschemacher, A. G. (2014) · Nature Communications · doi:10.1038/ncomms4284 · Cited by 340 · see citing works
Sirover, M. A. (2005) · Journal of Cellular Biochemistry · doi:10.1002/jcb.20399 · Cited by 321 · see citing works
Brown, A. M. (2004) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2004.02421.x · Cited by 308 · see citing works
Wiśniewski, J. R., & Mann, M. (2012) · Analytical Chemistry · doi:10.1021/ac300006b · Cited by 300 · see citing works
Self-citationMultifunctional role of astrocytes as gatekeepers of neuronal energy supply
Stobart, J. L., & Anderson, C. M. (2013) · Frontiers in Cellular Neuroscience · doi:10.3389/fncel.2013.00038 · Cited by 266 · see citing works
Loaiza, A., Porras, O. H., & Barros, L. F. (2003) · The Journal of Neuroscience · doi:10.1523/jneurosci.23-19-07337.2003 · Cited by 254 · see citing works
Cerbai, F., Lana, D., Nosi, D., Petkova-Kirova, P., Zecchi, S., Brothers, H. M., Wenk, G. L., & Giovannini, M. G. (2012) · PLoS ONE · doi:10.1371/journal.pone.0045250 · Cited by 251 · see citing works
Extensive quantitative remodeling of the proteome between normal colon tissue and adenocarcinoma
Wiśniewski, J. R., Ostasiewicz, P., Duś, K., Zielińska, D. F., Gnad, F., & Mann, M. (2012) · Molecular Systems Biology · doi:10.1038/msb.2012.44 · Cited by 248 · see citing works
Self-citationChoi, H. B., Gordon, G. R., Zhou, N., Tai, C., Rungta, R. L., Martinez, J., Milner, T. A., Ryu, J. K., McLarnon, J. G., Tresguerres, M., et al. (2012) · Neuron · doi:10.1016/j.neuron.2012.08.032 · Cited by 242 · see citing works
PKM2 Regulates Chromosome Segregation and Mitosis Progression of Tumor Cells
Jiang, Y., Li, X., Yang, W., Hawke, D. H., Zheng, Y., Xia, Y., Aldape, K., Wei, C., Guo, F., Chen, Y., et al. (2013) · Molecular Cell · doi:10.1016/j.molcel.2013.11.001 · Cited by 237 · see citing works
Control of glycogen deposition
Ferrer, J. C., Favre, C., Gomis, R. R., Fernández-Novell, J. M., Garcı́a-Rocha, M., de la Iglesia, N., Cid, E., & Guinovart, J. J. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00565-9 · Cited by 234 · see citing works
Neurons Have an Active Glycogen Metabolism that Contributes to Tolerance to Hypoxia
Sáez, I., Durán, J., Sinadinos, C., Beltran, A., Yanes, Ó., Tevy, M. F., Martínez-Pons, C., Milán, M., & Guinovart, J. J. (2014) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1038/jcbfm.2014.33 · Cited by 211 · see citing works
Pyruvate kinase M2 and cancer: an updated assessment
Iqbal, M. A., Gupta, V., Prakasam, G., Mazurek, S., & Bamezai, R. N. K. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.04.011 · Cited by 189 · see citing works
Isolation of fructose diphosphate aldolases A, B, and C
Penhoet, E. E., Kochman, M., & Rutter, W. J. (1969) · Biochemistry · doi:10.1021/bi00839a025 · Cited by 186 · see citing works
Bittner, C. X., Valdebenito, R., Ruminot, I., Loaiza, A., Larenas, V., Sotelo-Hitschfeld, T., Moldenhauer, H. J., Martín, A. S., Gutiérrez, R., Zambrano, M., et al. (2011) · Journal of Neuroscience · doi:10.1523/jneurosci.5311-10.2011 · Cited by 186 · see citing works
A review of animal phosphofructokinase isozymes with an emphasis on their physiological role
Dunaway, G. (1983) · Molecular and Cellular Biochemistry · doi:10.1007/bf00230589 · Cited by 168 · see citing works
Molecular and catalytic properties of aldolase C
Penhoet, E. E., Kochman, M., & Rutter, W. J. (1969) · Biochemistry · doi:10.1021/bi00839a026 · Cited by 166 · see citing works
Pfeiffer-Guglielmi, B., Fleckenstein, B. T., Jung, G., & Hamprecht, B. (2003) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2003.01644.x · Cited by 159 · see citing works
Wiśniewski, J. R., Duś‐Szachniewicz, K., & Mann, M. (2012) · PROTEOMICS - CLINICAL APPLICATIONS · doi:10.1002/prca.201200046 · Cited by 149 · see citing works
Self-citationNeuronal inhibition of astroglial cell proliferation is membrane mediated.
Hatten, M. E. (1987) · The Journal of Cell Biology · doi:10.1083/jcb.104.5.1353 · Cited by 148 · see citing works
Solaz-Fuster, M. C., Gimeno-Alcañiz, J. V., R�os, S., Fernández-Sánchez, M. E., García-Fojeda, B., Criado‐García, O., Vı́lchez, D., Domínguez, J. E., Garcı́a-Rocha, M., Sánchez‐Piris, M., et al. (2007) · Human Molecular Genetics · doi:10.1093/hmg/ddm339 · Cited by 146 · see citing works
Brix, B., Mesters, J. R., Pellerin, L., & Jöhren, O. (2012) · Journal of Neuroscience · doi:10.1523/jneurosci.0879-12.2012 · Cited by 103 · see citing works
Mukai, T., Joh, K., Arai, Y., et al. (1986) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)35789-7 · Cited by 79 · see citing works
Purity, cell viability, expression of GFAP and bystin in astrocytes cultured by different procedures
Du, F., Qian, Z., Zhu, L., et al. (2009) · Journal of Cellular Biochemistry · doi:10.1002/jcb.22375 · Cited by 71 · see citing works
Anđjus, P. R., Stević-Marinković, Z., & Cherubim, E. (1997) · The Journal of Physiology · doi:10.1111/j.1469-7793.1997.103bf.x · Cited by 66 · see citing works
Nuclear localization of aldolase A correlates with cell proliferation
Mamczur, P., Gamian, A., Kołodziej, J., et al. (2013) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2013.07.013 · Cited by 63 · see citing works
Self-citationCrerar, M. M., Karlsson, O. P., Fletterick, R. J., & Hwang, P. K. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.23.13748 · Cited by 55 · see citing works
Serres, S., Bezançon, E., Franconi, J., & Merle, M. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m409429200 · Cited by 52 · see citing works
Regulation of glycogen synthase activity and phosphorylation by exercise
Nielsen, J. N., & Wojtaszewski, J. F. P. (2004) · Proceedings of The Nutrition Society · doi:10.1079/pns2004348 · Cited by 51 · see citing works
Wang, W., Wang, L., Endoh, A., Hummelke, G. C., Hawks, C. L., & Hornsby, P. J. (2005) · Journal of Endocrinology · doi:10.1677/joe.1.05909 · Cited by 38 · see citing works
Dringen, R., & Hamprecht, B. (1993) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.1993.tb03313.x · Cited by 29 · see citing works
Neurones express glutamine synthetase when deprived of glutamine or interaction with astrocytes
Fernandes, S. P., Dringen, R., Lawen, A., & Robinson, S. R. (2010) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2010.06869.x · Cited by 27 · see citing works
The effect of glycogen phosphorolysis on basal glutaminergic transmission
Mozrzymas, J. W., Szczęsny, T. J., & Rakus, D. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.12.033 · Cited by 27 · see citing works
Self-citationCell cycle-dependent expression and subcellular localization of fructose 1,6-bisphosphatase
Mamczur, P., Sok, A. J., Rzechonek, A., et al. (2011) · Histochemistry and Cell Biology · doi:10.1007/s00418-011-0884-1 · Cited by 24 · see citing works
Self-citationOvádi, J., Aragón, J. J., & Sols, A. (1986) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(86)91006-5 · Cited by 24 · see citing works
Aldolase A is present in smooth muscle cell nuclei.
Mamczur, P., & Dżugaj, A. (2008) · Acta Biochimica Polonica · doi:10.18388/abp.2008_3043 · Cited by 20 · see citing works
Self-citationKowalski, W., Nocon, D., Gamian, A., Kołodziej, J., & Rakus, D. (2012) · Journal of Cellular Physiology · doi:10.1002/jcp.22998 · Cited by 16 · see citing works
Self-citationNuclear Localization of Brain-type Glycogen Phosphorylase in Some Gastrointestinal Carcinoma
Uno, K., Shimada, S., Tsuruta, J., et al. (1998) · The Histochemical Journal · doi:10.1023/a:1003239302471 · Cited by 13 · see citing works
Nuclear localization of aldolase A in pig cardiomyocytes.
Mamczur, P., & Dżugaj, A. (2004) · PubMed · doi:10.14670/hh-19.753 · Cited by 13 · see citing works
Self-citationZeitschel, U., Schliebs, R., Roßner, S., et al. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.01127.x · Cited by 12 · see citing works
Urbano, F. J., Sierra, F., Velasco, J. M., & Bu�o, W. (1997) · Glia · doi:10.1002/(sici)1098-1136(199705)20:1 · Cited by 3 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Lactate in the brain: from metabolic end-product to signalling molecule
Magistretti, P. J., & Allaman, I. (2018) · Nature Reviews Neuroscience · doi:10.1038/nrn.2018.19 · Cited by 1,298 · see citing works
A Cellular Perspective on Brain Energy Metabolism and Functional Imaging
Magistretti, P. J., & Allaman, I. (2015) · Neuron · doi:10.1016/j.neuron.2015.03.035 · Cited by 1,285 · see citing works
Fueling thought: Management of glycolysis and oxidative phosphorylation in neuronal metabolism
Yellen, G. (2018) · Journal of Cell Biology · doi:10.1083/jcb.201803152 · Cited by 371 · see citing works
“In vitro glycolytic behavior can change with choice of culture media (Sünwoldt et al., 2017) and astrocyte coculture (Mamczur et al., 2015), but gene expression data from acutely dissociated brain cells indicate that neurons are well equipped for glycolysis, with higher levels of mRNA expression…”
BackgroundNon-Canonical Control of Neuronal Energy Status by the Na+ Pump
Baeza-Lehnert, F., Saab, A. S., Gutiérrez, R., Larenas, V., Díaz, E., Horn, M., Vargas, M., Hösli, L., Stobart, J., Hirrlinger, J., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2018.11.005 · Cited by 126 · see citing works
New astroglial injury-defined biomarkers for neurotrauma assessment
Halford, J., Shen, S., Itamura, K., Levine, J., Chong, A. C., Czerwieniec, G., Glenn, T. C., Hovda, D. A., Vespa, P., Bullock, R., et al. (2017) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1177/0271678x17724681 · Cited by 75 · see citing works
Zhao, J., Ikezu, T. C., Lu, W., Macyczko, J. R., Li, Y., Lewis-Tuffin, L. J., Martens, Y. A., Ren, Y., Zhu, Y., Asmann, Y. W., et al. (2023) · Stem Cell Research & Therapy · doi:10.1186/s13287-023-03444-y · Cited by 25 · see citing works
- Authors
- Mamczur, P., Borsuk, B., Paszko, J., Sas, Z., Mozrzymas, J., Wiśniewski, J. R., Gizak, A., & Rakus, D.
- Affiliations
- University of Wrocław (PL)
- Max Planck Institute of Biochemistry (DE)
- Corresponding author
- Rakus, Dariusz
- Venue
- Glia
- Publisher
- Wiley
- Published
- 2014-09-24
- Volume
- 63
- Issue
- 2
- Pages
- 328-340
- ISSN
- 0894-1491 (ISSN-L)
- 1098-1136
- OpenAlex
- W1952806621
- Cited by
- 71
- References
- 57
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 2 · 2023: 6 · 2022: 7 · 2021: 5 · 2020: 9 · 2019: 7 · 2018: 11 · 2017: 4 · 2016: 5 · 2015: 8
- FWCI
- 2.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Glia (publishedVersion)
- PubMed (publishedVersion)
- Max Planck Digital Library (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Polish Ministry of Science and Higher Education (#N303815540)
- Experimental Biology Institute of Wrocław University
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Keywords
- astrocyte-neuron crosstalk, astrocyte metabolism, carbohydrate metabolism enzymes, glycolysis, glycogen metabolism, glutamine metabolism, lactate, glutamine synthetase, phosphofructokinase, aldolase, pyruvate kinase, glycogen synthase, glycogen phosphorylase, subcellular localization, nuclear localization, astrocyte proliferation, hippocampal astrocytes, co-culture
- MeSH terms
- Actins, Animals, Animals, Newborn, Astrocytes, Cells, Cultured, Fructose-Bisphosphate Aldolase, Glycogen Synthase, Hippocampus, Neurons, Pyruvate Kinase, Subcellular Fractions, Culture Media, Conditioned, Rats, Wistar, Coculture Techniques, Proteomics, Carbohydrate Metabolism, Rats
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review