Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Fructose 1,6-Bisphosphatase 2-Camk2 Interaction Is an Integral Mechanism of Long-Term Potentiation

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. Preprints 2020, 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.

Subject Areas

memory formation; moonlighting protein; protein-protein interaction; astrocyte-neuron lactate shuttle

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