Brain‐derived neurotrophic factor‐induced regulation of RNA metabolism in neuronal development and synaptic plasticity

• Published in: Wiley interdisciplinary reviews. RNA 2022-09, Vol.13 (5), p.e1713-n/a
• Main Authors: Costa, Rui O., Martins, Luís F., Tahiri, Emanuel, Duarte, Carlos B.
• Format: Article
• Language: English
• Subjects: Brain-derived neurotrophic factor; Developmental plasticity; Developmental stages; intracellular signaling; local protein synthesis; Localization; Nervous system; neuronal development; Neuroplasticity; Potentiation; Presynaptic plasticity; Protein biosynthesis; Protein composition; Protein structure; Protein synthesis; Proteins; Proteomes; Ribonucleic acid; RNA; RNA binding proteins; RNA transport; Structure-function relationships; Synaptic plasticity; Synaptogenesis; TrkB receptors; Tropomyosin
• ISSN: 1757-7004; 1757-7012
• DOI: 10.1002/wrna.1713

The neurotrophin brain‐derived neurotrophic factor (BDNF) plays multiple roles in the nervous system, including in neuronal development, in long‐term synaptic potentiation in different brain regions, and in neuronal survival. Alterations in these regulatory mechanisms account for several diseases of the nervous system. The synaptic effects of BDNF mediated by activation of tropomyosin receptor kinase B (TrkB) receptors are partly mediated by stimulation of local protein synthesis which is now considered a ubiquitous feature in both presynaptic and postsynaptic compartments of the neuron. The capacity to locally synthesize proteins is of great relevance at several neuronal developmental stages, including during neurite development, synapse formation, and stabilization. The available evidence shows that the effects of BDNF–TrkB signaling on local protein synthesis regulate the structure and function of the developing and mature synapses. While a large number of studies have illustrated a wide range of effects of BDNF on the postsynaptic proteome, a growing number of studies also point to presynaptic effects of the neurotrophin in the local regulation of the protein composition at the presynaptic level. Here, we will review the latest evidence on the role of BDNF in local protein synthesis, comparing the effects on the presynaptic and postsynaptic compartments. Additionally, we overview the relevance of BDNF‐associated local protein synthesis in neuronal development and synaptic plasticity, at the presynaptic and postsynaptic compartments, and their relevance in terms of disease. This article is categorized under: RNA Interactions with Proteins and Other Molecules > Protein‐RNA Interactions: Functional Implications RNA Export and Localization > RNA Localization BDNF–TrkB signaling promotes the release of mRNAs from the RNA binding proteins responsible for their trafficking (1). Then, these mRNAs become readily available for translation. This local protein synthesis (2) is highly relevant and directly involved in axonal and dendritic maturation, and in synaptic function.