In this Research Topic we seek to gather submission of reviews and original research articles on the role of PI3K/Pten-mTOR signaling in neurobiology. The PI3K-mTOR pathway enhances growth and motility in divergent cell types and has been conserved since its augmentation by unicellular organisms. Consistent with its role in growth and survival, dysregulation of the PI3K/Pten-mTOR cascade has been repeatedly implicated in both cancer and non-cancerous tumour disorders. However, implementation of the PI3K/Pten-mTOR pathway for the specialized growth requirements of neurons is carried out in a unique cellular context and dysregulation of this pathway has been implicated in neurological disorders. A central goal then is to elucidate the unique mechanisms through which PI3K/Pten-mTOR signalling affects neuronal function. We intend for the scope of this topic to be comprehensive, including regulators of pathway activation, inhibition, and modulation. The mechanisms whereby the activation of the PI3K-mTOR pathway regulates processes such as cytoskeletal polymerization, translation and trafficking of synaptic proteins, and neurotransmitter release and reception are fundamental to cellular neurobiology. Receptor tyrosine kinases transduce the extracellular influence of growth factors, ephrins and other factors through the Ras/PI3K-mTOR pathway (as-well-as the PLCgamma pathway). G-protein coupled receptors such as group 1 metabatropic glutamate receptors also activate Ras/PI3K-mTOR signalling. Opposing this signalling, the phosphatase and tensin homolog (PTEN) catalyzes the reverse reaction of PI3K regulating the phosphorylation state of phosphatidylinositides - impacting membrane lipids, ion channels, cytoskeletal components, and downstream Akt and mTOR activation. Other negative modulators of the PI3K/Pten-mTOR pathway include Neurofibromin-1 (NF1; a GTPase activating protein regulating Ras/mTOR activation) and Tuberous Sclerosis 1 and 2 (aka hamartin and tuberin respsectively; GTPase activating proteins that oppose downstream mTOR signaling). An important effect of PI3K-mTOR activation is to activate translation via ribosomal S6-kinase and 4E-BP1/eIF4E. Further, many targets activated by mTOR are regulated by fragile x mental retardation protein (FMRP). Notably, all of these related proteins have been demonstrated to impact neuronal growth, synapse formation, and synapse function, and they have been implicated in the pathophysiology of disorders such as autism, epilepsy, and intellectual disability. In this Research Topic we aim to provide an analysis and perspective of research that addresses how PI3K/Pten-mTOR signaling influences both normal and pathological neuronal function.
In this Research Topic we seek to gather submission of reviews and original research articles on the role of PI3K/Pten-mTOR signaling in neurobiology. The PI3K-mTOR pathway enhances growth and motility in divergent cell types and has been conserved since its augmentation by unicellular organisms. Consistent with its role in growth and survival, dysregulation of the PI3K/Pten-mTOR cascade has been repeatedly implicated in both cancer and non-cancerous tumour disorders. However, implementation of the PI3K/Pten-mTOR pathway for the specialized growth requirements of neurons is carried out in a unique cellular context and dysregulation of this pathway has been implicated in neurological disorders. A central goal then is to elucidate the unique mechanisms through which PI3K/Pten-mTOR signalling affects neuronal function. We intend for the scope of this topic to be comprehensive, including regulators of pathway activation, inhibition, and modulation. The mechanisms whereby the activation of the PI3K-mTOR pathway regulates processes such as cytoskeletal polymerization, translation and trafficking of synaptic proteins, and neurotransmitter release and reception are fundamental to cellular neurobiology. Receptor tyrosine kinases transduce the extracellular influence of growth factors, ephrins and other factors through the Ras/PI3K-mTOR pathway (as-well-as the PLCgamma pathway). G-protein coupled receptors such as group 1 metabatropic glutamate receptors also activate Ras/PI3K-mTOR signalling. Opposing this signalling, the phosphatase and tensin homolog (PTEN) catalyzes the reverse reaction of PI3K regulating the phosphorylation state of phosphatidylinositides - impacting membrane lipids, ion channels, cytoskeletal components, and downstream Akt and mTOR activation. Other negative modulators of the PI3K/Pten-mTOR pathway include Neurofibromin-1 (NF1; a GTPase activating protein regulating Ras/mTOR activation) and Tuberous Sclerosis 1 and 2 (aka hamartin and tuberin respsectively; GTPase activating proteins that oppose downstream mTOR signaling). An important effect of PI3K-mTOR activation is to activate translation via ribosomal S6-kinase and 4E-BP1/eIF4E. Further, many targets activated by mTOR are regulated by fragile x mental retardation protein (FMRP). Notably, all of these related proteins have been demonstrated to impact neuronal growth, synapse formation, and synapse function, and they have been implicated in the pathophysiology of disorders such as autism, epilepsy, and intellectual disability. In this Research Topic we aim to provide an analysis and perspective of research that addresses how PI3K/Pten-mTOR signaling influences both normal and pathological neuronal function.
