Fructose 1,6-Bisphosphatase 2 Plays a Crucial Role in the Induction and Maintenance of Long-Term Potentiation
Long-term potentiation (LTP) is a molecular basis of memory formation. Here, we demonstrate that LTP critically depends on fructose 1,6-bisphosphatase 2 (Fbp2)—a glyconeogenic enzyme and moonlighting protein protecting mitochondria against stress. We show that LTP induction regulates Fbp2 associatio...
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2020-06-01
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| Online Access: | https://www.mdpi.com/2073-4409/9/6/1375 |
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| author | Przemysław Duda Tomasz Wójtowicz Jakub Janczara Daniel Krowarsch Aleksandra Czyrek Agnieszka Gizak Dariusz Rakus |
| author_facet | Przemysław Duda Tomasz Wójtowicz Jakub Janczara Daniel Krowarsch Aleksandra Czyrek Agnieszka Gizak Dariusz Rakus |
| author_sort | Przemysław Duda |
| collection | DOAJ |
| description | Long-term potentiation (LTP) is a molecular basis of memory formation. Here, we demonstrate that LTP critically depends on fructose 1,6-bisphosphatase 2 (Fbp2)—a glyconeogenic enzyme and moonlighting protein protecting mitochondria against stress. We show that LTP induction regulates Fbp2 association with neuronal mitochondria and Camk2 and that the Fbp2–Camk2 interaction correlates with Camk2 autophosphorylation. Silencing of Fbp2 expression or simultaneous inhibition and tetramerization of the enzyme with a synthetic effector mimicking the action of physiological inhibitors (NAD<sup>+</sup> and AMP) abolishes Camk2 autoactivation and blocks formation of the early phase of LTP and expression of the late phase LTP markers. Astrocyte-derived lactate reduces NAD<sup>+</sup>/NADH ratio in neurons and thus diminishes the pool of tetrameric and increases the fraction of dimeric Fbp2. We therefore hypothesize that this NAD<sup>+</sup>-level-dependent increase of the Fbp2 dimer/tetramer ratio might be a crucial mechanism in which astrocyte–neuron lactate shuttle stimulates LTP formation. |
| first_indexed | 2024-03-10T19:26:20Z |
| format | Article |
| id | doaj.art-fa4b94fa9b104d83bc0cc5ebe57b5e43 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T19:26:20Z |
| publishDate | 2020-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-fa4b94fa9b104d83bc0cc5ebe57b5e432023-11-20T02:32:35ZengMDPI AGCells2073-44092020-06-0196137510.3390/cells9061375Fructose 1,6-Bisphosphatase 2 Plays a Crucial Role in the Induction and Maintenance of Long-Term PotentiationPrzemysław Duda0Tomasz Wójtowicz1Jakub Janczara2Daniel Krowarsch3Aleksandra Czyrek4Agnieszka Gizak5Dariusz Rakus6Department of Molecular Physiology and Neurobiology, University of Wrocław, 50-335 Wrocław, PolandLaboratory of Cell Biophysics, Nencki Institute of Experimental Biology, Polish Academy of Sciences, 02-093 Warsaw, PolandDepartment of Molecular Physiology and Neurobiology, University of Wrocław, 50-335 Wrocław, PolandDepartment of Protein Biotechnology, University of Wrocław, 50-383 Wrocław, PolandDepartment of Protein Biotechnology, University of Wrocław, 50-383 Wrocław, PolandDepartment of Molecular Physiology and Neurobiology, University of Wrocław, 50-335 Wrocław, PolandDepartment of Molecular Physiology and Neurobiology, University of Wrocław, 50-335 Wrocław, PolandLong-term potentiation (LTP) is a molecular basis of memory formation. Here, we demonstrate that LTP critically depends on fructose 1,6-bisphosphatase 2 (Fbp2)—a glyconeogenic enzyme and moonlighting protein protecting mitochondria against stress. We show that LTP induction regulates Fbp2 association with neuronal mitochondria and Camk2 and that the Fbp2–Camk2 interaction correlates with Camk2 autophosphorylation. Silencing of Fbp2 expression or simultaneous inhibition and tetramerization of the enzyme with a synthetic effector mimicking the action of physiological inhibitors (NAD<sup>+</sup> and AMP) abolishes Camk2 autoactivation and blocks formation of the early phase of LTP and expression of the late phase LTP markers. Astrocyte-derived lactate reduces NAD<sup>+</sup>/NADH ratio in neurons and thus diminishes the pool of tetrameric and increases the fraction of dimeric Fbp2. We therefore hypothesize that this NAD<sup>+</sup>-level-dependent increase of the Fbp2 dimer/tetramer ratio might be a crucial mechanism in which astrocyte–neuron lactate shuttle stimulates LTP formation.https://www.mdpi.com/2073-4409/9/6/1375memory formationmoonlighting proteinprotein–protein interactionastrocyte-neuron lactate shuttle |
| spellingShingle | Przemysław Duda Tomasz Wójtowicz Jakub Janczara Daniel Krowarsch Aleksandra Czyrek Agnieszka Gizak Dariusz Rakus Fructose 1,6-Bisphosphatase 2 Plays a Crucial Role in the Induction and Maintenance of Long-Term Potentiation Cells memory formation moonlighting protein protein–protein interaction astrocyte-neuron lactate shuttle |
| title | Fructose 1,6-Bisphosphatase 2 Plays a Crucial Role in the Induction and Maintenance of Long-Term Potentiation |
| title_full | Fructose 1,6-Bisphosphatase 2 Plays a Crucial Role in the Induction and Maintenance of Long-Term Potentiation |
| title_fullStr | Fructose 1,6-Bisphosphatase 2 Plays a Crucial Role in the Induction and Maintenance of Long-Term Potentiation |
| title_full_unstemmed | Fructose 1,6-Bisphosphatase 2 Plays a Crucial Role in the Induction and Maintenance of Long-Term Potentiation |
| title_short | Fructose 1,6-Bisphosphatase 2 Plays a Crucial Role in the Induction and Maintenance of Long-Term Potentiation |
| title_sort | fructose 1 6 bisphosphatase 2 plays a crucial role in the induction and maintenance of long term potentiation |
| topic | memory formation moonlighting protein protein–protein interaction astrocyte-neuron lactate shuttle |
| url | https://www.mdpi.com/2073-4409/9/6/1375 |
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