Version 1
: Received: 30 April 2020 / Approved: 5 May 2020 / Online: 5 May 2020 (06:09:47 CEST)
How to cite:
Duda, P.; Wójtowicz, T.; Janczara, J.; Krowarsch, D.; Czyrek, A.; Gizak, A.; Rakus, D. Fructose 1,6-Bisphosphatase 2-Camk2 Interaction Is an Integral Mechanism of Long-Term Potentiation. Preprints2020, 2020050065 (doi: 10.20944/preprints202005.0065.v1).
Duda, P.; Wójtowicz, T.; Janczara, J.; Krowarsch, D.; Czyrek, A.; Gizak, A.; Rakus, D. Fructose 1,6-Bisphosphatase 2-Camk2 Interaction Is an Integral Mechanism of Long-Term Potentiation. Preprints 2020, 2020050065 (doi: 10.20944/preprints202005.0065.v1).
Cite as:
Duda, P.; Wójtowicz, T.; Janczara, J.; Krowarsch, D.; Czyrek, A.; Gizak, A.; Rakus, D. Fructose 1,6-Bisphosphatase 2-Camk2 Interaction Is an Integral Mechanism of Long-Term Potentiation. Preprints2020, 2020050065 (doi: 10.20944/preprints202005.0065.v1).
Duda, P.; Wójtowicz, T.; Janczara, J.; Krowarsch, D.; Czyrek, A.; Gizak, A.; Rakus, D. Fructose 1,6-Bisphosphatase 2-Camk2 Interaction Is an Integral Mechanism of Long-Term Potentiation. Preprints 2020, 2020050065 (doi: 10.20944/preprints202005.0065.v1).
Abstract
Long-term potentiation (LTP) is a molecular basis of memory formation. Here, we demonstrate that LTP critically depends on muscle 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+ 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+/NADH ratio in neurons and thus, diminishes the pool of tetrameric and increases the fraction of dimeric Fbp2. We therefore hypothesize that this NAD+-level-dependent increase of the Fbp2 dimer/tetramer ratio might be a crucial mechanism in which astrocyte-neuron lactate shuttle stimulates LTP formation.
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Przemysław Duda
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