Feb 20, 2020

Endoplasmic reticulum (ER) lumenal indicators in Drosophila reveal effects of HSP-related mutations on ER calcium dynamics

BioRxiv : the Preprint Server for Biology
Megan Kate OlivaCahir J. O'Kane

Abstract

Genes for 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 ro...Continue Reading

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Mentioned in this Paper

Calcium
Abnormal Degeneration
Genes
Physiological Aspects
GAL4 protein, Drosophila
Gene Mutant
Larva
Calcium ion
Homologous Gene
SPG11 protein, human

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