Expression of Fbp2, a Newly Discovered Constituent of Memory Formation Mechanisms, Is Regulated by Astrocyte–Neuron Crosstalk

Abstract

Fbp2 (muscle isozyme of fructose 1,6-bisphosphatase) is a glyconeogenesis-regulating enzyme and a multifunctional protein indispensable for long-term potentiation (LTP) formation in the hippocampus. Here, we present evidence that expression of Fbp2 in murine hippocampal cell cultures is regulated by crosstalk between neurons and astrocytes. Co-culturing of the two cell types results in a decrease in Fbp2 expression in astrocytes, and its simultaneous increase in neurons, as compared to monocultures. These changes are regulated by paracrine signaling using extracellular vesicle (EV)-packed factors released to the culture medium. It is well accepted that astrocyte–neuron metabolic crosstalk plays a crucial role in shaping neuronal function, and recently we have suggested that Fbp2 is a hub linking neuronal signaling with redox and/or energetic state of brain during the formation of memory traces. Thus, our present results emphasize the importance of astrocyte–neuron crosstalk in the regulation of the cells’ metabolism and synaptic plasticity, and bring us one step closer to a mechanistic understanding of the role of Fbp2 in these processes.

Cobalt Regulates Activation of Camk2α in Neurons by Influencing Fructose 1,6-Bisphosphatase 2 Quaternary Structure and Subcellular Localization

“…Fbp2 is also the predominant form of the enzyme in neurons [ 2 ]. Aside from regulation of glycogen synthesis from carbohydrate precursors, Fbp2, as a moonlighting protein, is engaged in cell cycle-dependent events [ 1 ], activation of synaptic plasticity phenomena [ 2 ], and regulation of activity of transcriptional factors [ 3 , 4 , 5 , 6 ]. It has been demonstrated that Fbp2 protects mitochondria against stress conditions such as a high level of calcium and its consequences (mitochondrial swelling and decreased ATP synthesis) [ 2 , 7 ].…”

“…Fbp2 may be translocated to the cell nucleus in a hormone-dependent manner [ 12 ] where it regulates transcriptional activities of c-Myc and Hif1α [ 3 , 4 , 5 , 6 ]. Recently, Fbp2 has been shown to regulate synaptic plasticity by influencing the induction and maintenance of early and late phases of long-term potentiation (LTP).…”