Endoplasmic Reticulum Lumenal Indicators in Drosophila Reveal Effects of HSP-Related Mutations on Endoplasmic Reticulum Calcium Dynamics
| Autor: | Cahir J. O'Kane, Trevor J. Wardill, Megan K Oliva, Jillian O'Shaughnessy, Juan José Pérez-Moreno |
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| Přispěvatelé: | Perez Moreno, Juan [0000-0002-8497-3066], O'Kane, Cahir [0000-0002-3488-2078], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Mutant lcsh:RC321-571 03 medical and health sciences 0302 clinical medicine Calcium imaging medicine Axon hereditary spastic paraplegia lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry Chemistry General Neuroscience Endoplasmic reticulum Neurodegeneration Wild type neurodegeneration medicine.disease Phenotype 3. Good health Cell biology endoplasmic reticulum calcium imaging 030104 developmental biology medicine.anatomical_structure Reticulon Drosophila 030217 neurology & neurosurgery Neuroscience |
| Zdroj: | Frontiers in Neuroscience, Vol 14 (2020) Frontiers in Neuroscience |
| Popis: | Genes for endoplasmic reticulum (ER)-shaping proteins are among the most commonly mutated in hereditary spastic paraplegia (HSP). Mutation of these genes in model organisms can lead to disruption of the ER network. To investigate how the physiological roles of the ER might be affected by such disruption, we developed tools to interrogate its Ca2+ signaling function. We generated GAL4-driven Ca2+ sensors targeted to the ER lumen, to record ER Ca2+ fluxes in identified Drosophila neurons. Using GAL4 lines specific for Type Ib or Type Is larval motor neurons, we compared the responses of different lumenal indicators to electrical stimulation, in axons and presynaptic terminals. The most effective sensor, ER-GCaMP6-210, had a Ca2+ affinity close to the expected ER lumenal concentration. Repetitive nerve stimulation generally showed a transient increase of lumenal Ca2+ in both the axon and presynaptic terminals. Mutants lacking neuronal reticulon and REEP proteins, homologs of human HSP proteins, showed a larger ER lumenal evoked response compared to wild type; we propose mechanisms by which this phenotype could lead to neuronal dysfunction or degeneration. Our lines are useful additions to a Drosophila Ca2+ imaging toolkit, to explore the physiological roles of ER, and its pathophysiological roles in HSP and in axon degeneration more broadly. |
| Databáze: | OpenAIRE |
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