NG2 cells as receivers and transducers of neuronal network signals via locally translated mRNA
Final Report Abstract
Oligodendrocyte Precursor Cells, OPC (characteristically expressing the NG2 proteoglycan) are a very interesting population of glial cells, unique in forming synapses with neurons. In addition to their well-described role of acting as precursors to myelinating oligodendrocytes, work from our own group and others has shown that they have additional roles. These include the synthesis of neuromodulatory factors and the ability to modulate glutamergic signalling of nearby neurons via the release of the ectodomain of the NG2 protein, which binds to adjacent neurons. Many cell types utilize local translation of localized mRNAs to allow fast fine-tuning of local protein synthesis. This can be at the leading edge of a fibroblast where actin mRNA is locally translated, or at synapses between neurons where many mRNAs are localized and translated “on demand” in response to specific signals.. Prior to such local translation, the mRNAs must first be transported to the specific sites where they are stored until needed. The aim of our project was to characterise process- and synapse-localised mRNAs in NG2 cells and the regulation of their translation into protein in response to neuronal network signalling. We focussed on three candidates: Histone 3.3a and Olig1 and Olig 2 which we had identified in a previous screen. Using in situ hybridization (FISH) on NG2+ cells acutely isolated from early postnatal brains, we showed that the Histone 3f3a mRNA, Olig 1 and Olig 2 mRNAs and ribosomes are localized in the cell processes. We could also visualize these process-localised mRNAs on brain sections of juvenile mice. We identified distinct stimulation conditions which caused the synthesis of protein from these localised mRNAs in cultured NG2 cells. We identified a potential protein partner binding to the Histone mRNA and regulating its function.
Publications
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GLIAL DEVELOPMENT AND PLASTICITY at the Cold Spring Harbor Glia in Health and Disease 2018. “Activitydependent translation of localized mRNAs in glia—NG2 cells as receivers and transducers of neuronal network signals”
Jacqueline Trotter, Hatice Yigit, Vanessa Hübner, Anke Müller & Daniela Dieterich
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Diversity in the Oligodendrocyte Lineage: Current Evidence. Neuron, 101(3), 356-357.
Trotter, Jacqueline & Mittmann, Thomas
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Early life adversity targets the transcriptional signature of hippocampal NG2+ glia and affects voltage gated sodium (Nav) channels properties. Neurobiology of Stress, 15, 100338.
Treccani, Giulia; Yigit, Hatice; Lingner, Thomas; Schleuβner, Vanessa; Mey, Franziska; van der Kooij, Michael A.; Wennström, Malin; Herzog, David P.; Linke, Matthias; Fricke, Markus; Schmeisser, Michael J.; Wegener, Gregers; Mittmann, Thomas; Trotter, Jacqueline & Müller, Marianne B.
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Early Life Stress Programming of NG2+ Glia Transcriptome Alters Functional Properties of Voltage Gated Sodium (Nav) Channels and Cognitive Performance. Biological Psychiatry, 89(9), S117-S118.
Treccani, Giulia; Yigit, Hatice; Lingner, Thomas; Schleuβner, Vanessa; Wennström, Malin; Herzog, David; Fricke, Markus; Wegener, Gregers; Mittmann, Thomas; Trotter, Jacqueline & Müller, Marianne
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Kloster Schoental 2021 University of Heidelberg IZN Retreat. “NG2 glia: receivers and transducers of neuronal network signals”
Jacqueline Trotter
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Gordon Research conference on Myelin, Lucca, Italy May 2022: Signaling Between Neurons and NG2 Glia: Glial Signal Integration and Protein Synthesis
Vanessa Schleußner, Hatice Yigit, Thomas Mittmann & Jacqueline Trotter
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Klaus Nave lab MPI Göttingen Dept. of Neurogenetics Lab retreat June 13th.-17th. 2022 Störmthaler See, near Leipzig. “NG2+ cells as receivers and transducers of neuronal network signals”
Jacqueline Trotter
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Retreat International Masters Program in Biomedicine University of Mainz (with Luxembourg and Strasbourg Universities) Boppard, Germany October 4th-7th 2023 “NG2+ cells as receivers and transducers of neuronal network signals”
Jacqueline Trotter
