Dscam2 suppresses synaptic strength through a PI3K-dependent endosomal pathway
| Autor: | Peter G. Noakes, Lucy E. Harris, Nickolas A. Lavidis, Grace Ji-eun Shin, Sarah K. Kerwin, G. Lorenzo Odierna, S. Sean Millard |
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| Rok vydání: | 2019 |
| Předmět: |
Gene isoform
Neurite Endosome Neurogenesis Neuromuscular Junction Endosomes Biology Phosphatidylinositols Synaptic vesicle Synaptic Transmission Article Animals Genetically Modified Phosphatidylinositol 3-Kinases Microscopy Electron Transmission Peripheral Nervous System Extracellular Animals Drosophila Proteins Protein Isoforms Neural Cell Adhesion Molecules PI3K/AKT/mTOR pathway Phosphoinositide-3 Kinase Inhibitors Motor Neurons Phosphoinositide 3-kinase GTPase-Activating Proteins Membrane and Lipid Biology Cell Biology Immunohistochemistry Cell biology Larva Mutation biology.protein Drosophila Function (biology) Neuroscience |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 |
| Popis: | Dscam2 is a cell recognition molecule involved in many aspects of neurodevelopment. Here, Odierna et al. identify a new function for this protein in regulating synaptic strength. Dscam2 is a cell surface protein required for neuronal development in Drosophila; it can promote neural wiring through homophilic recognition that leads to either adhesion or repulsion between neurites. Here, we report that Dscam2 also plays a post-developmental role in suppressing synaptic strength. This function is dependent on one of two distinct extracellular isoforms of the protein and is autonomous to motor neurons. We link the PI3K enhancer, Centaurin gamma 1A, to the Dscam2-dependent regulation of synaptic strength and show that changes in phosphoinositide levels correlate with changes in endosomal compartments that have previously been associated with synaptic strength. Using transmission electron microscopy, we find an increase in synaptic vesicles at Dscam2 mutant active zones, providing a rationale for the increase in synaptic strength. Our study provides the first evidence that Dscam2 can regulate synaptic physiology and highlights how diverse roles of alternative protein isoforms can contribute to unique aspects of brain development and function. |
| Databáze: | OpenAIRE |
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