Neuronal fragile X mental retardation protein activates glial insulin receptor mediated PDF-Tri neuron developmental clearance
| Autor: | Cole J. Meier, Dominic J. Vita, Kendal Broadie |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Central Nervous System congenital hereditary and neonatal diseases and abnormalities Autism Spectrum Disorder Phagocytosis Receptor expression Science General Physics and Astronomy Context (language use) Biology General Biochemistry Genetics and Molecular Biology Article 03 medical and health sciences Fragile X Mental Retardation Protein 0302 clinical medicine Antigens CD medicine Biological neural network Animals Drosophila Proteins Neurons Multidisciplinary fungi Neuropeptides Insulin signalling General Chemistry Autism spectrum disorders medicine.disease Receptor Insulin nervous system diseases Fragile X syndrome Insulin receptor 030104 developmental biology medicine.anatomical_structure nervous system Fragile X Syndrome biology.protein Drosophila Neuron Neuroscience Neuroglia 030217 neurology & neurosurgery Function (biology) Signal Transduction |
| Zdroj: | Nature Communications Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021) |
| ISSN: | 2041-1723 |
| Popis: | Glia engulf and phagocytose neurons during neural circuit developmental remodeling. Disrupting this pruning process contributes to Fragile X syndrome (FXS), a leading cause of intellectual disability and autism spectrum disorder in mammals. Utilizing a Drosophila FXS model central brain circuit, we identify two glial classes responsible for Draper-dependent elimination of developmentally transient PDF-Tri neurons. We find that neuronal Fragile X Mental Retardation Protein (FMRP) drives insulin receptor activation in glia, promotes glial Draper engulfment receptor expression, and negatively regulates membrane-molding ESCRT-III Shrub function during PDF-Tri neuron clearance during neurodevelopment in Drosophila. In this context, we demonstrate genetic interactions between FMRP and insulin receptor signaling, FMRP and Draper, and FMRP and Shrub in PDF-Tri neuron elimination. We show that FMRP is required within neurons, not glia, for glial engulfment, indicating FMRP-dependent neuron-to-glia signaling mediates neuronal clearance. We conclude neuronal FMRP drives glial insulin receptor activation to facilitate Draper- and Shrub-dependent neuronal clearance during neurodevelopment in Drosophila. Glia are involved in remodelling of neural circuits during development. Here, the authors show that FMRP is required within neurons to activate glial insulin receptor to facilitate Draper- and Shrub-dependent neuronal clearance during neurodevelopment in Drosophila. |
| Databáze: | OpenAIRE |
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