The Signaling of neuregulin-epidermal growth factor receptors and its impact on the nervous system

Abstract The activation of members of the Epidermal Growth Factor Receptor (EGFR) family (including ErbB) triggers pathways that have significant effects on cellular processes and have profound consequences both in physiological and pathological conditions. Within the nervous system, the neuregulin (NRG)/ErbB3 signaling plays a crucial role in promoting the formation and maturation of excitatory synapses. Noteworthy is ErbB3, which is actively involved in the process of cerebellar lamination and myelination. All members of the ErbB-family, in particular ErbB3, have been observed within the nuclei of various cell types, including both full-length receptors and alternative variants. One of these variants was detected in Schwann cells and in glioblastoma primary cells where it showed a neuregulin-dependent expression. It binds to promoters’ chromatin associated with genes, like ezrin, involved in the formation of Ranvier’s node. Its nucleolar localization suggests that it may play a role in ribosome biogenesis and in cell proliferation. The regulation of ErbB3 expression is a complex and dynamic process that can be influenced by different factors, including miRNAs. This mechanism appears to play a significant role in glioblastoma and is often associated with a poor prognosis. Altogether, the targeting of ErbB3 has emerged as an active area of research in glioblastoma treatment. These findings highlight the underappreciated role of ErbB3 as a significant receptor that can potentially play a pivotal role in diverse pathologies, implying the existence of a shared and intricate mechanism that warrants further investigation. Keywords: ErbB receptors; ErbB3; glioblastoma; glioma; neuregulin; brain; nucleolus; nucleolin; miRNA; myelination; tyrosine kinase inhibitors