The sulfite oxidase Shopper controls neuronal activity by regulating glutamate homeostasis in Drosophila ensheathing glia

• Published in: Nature communications 2018-08, Vol.9 (1), p.3514-12, Article 3514
• Main Authors: Otto, Nils, Marelja, Zvonimir, Schoofs, Andreas, Kranenburg, Holger, Bittern, Jonas, Yildirim, Kerem, Berh, Dimitri, Bethke, Maria, Thomas, Silke, Rode, Sandra, Risse, Benjamin, Jiang, Xiaoyi, Pankratz, Michael, Leimkühler, Silke, Klämbt, Christian
• Format: Article
• Language: English
• Subjects: 13/44; 13/95; 14/19; 42/41; 42/89; 45/70; 631/378/1689; 631/378/2571/219; 631/378/2596; 631/378/548/1964; 64/24; Animals; Astrocytes; Astrocytes - metabolism; Central nervous system; Data processing; Drosophila; Drosophila Proteins - genetics; Drosophila Proteins - metabolism; Glial cells; Glutamates - metabolism; Head; Homeostasis; Homology; Humanities and Social Sciences; Information processing; Insects; Invertebrates; Mitochondria; multidisciplinary; Neural networks; Neuroglia - metabolism; Neuromodulation; Neuronal-glial interactions; Oligodendrocytes; Oxidase; Peristalsis; Science; Science (multidisciplinary); Seizures; Sulfite; Sulfite oxidase; Sulfite Oxidase - genetics; Sulfite Oxidase - metabolism; Sulfites - metabolism; Vertebrates
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-018-05645-z

Specialized glial subtypes provide support to developing and functioning neural networks. Astrocytes modulate information processing by neurotransmitter recycling and release of neuromodulatory substances, whereas ensheathing glial cells have not been associated with neuromodulatory functions yet. To decipher a possible role of ensheathing glia in neuronal information processing, we screened for glial genes required in the Drosophila central nervous system for normal locomotor behavior. Shopper encodes a mitochondrial sulfite oxidase that is specifically required in ensheathing glia to regulate head bending and peristalsis. shopper mutants show elevated sulfite levels affecting the glutamate homeostasis which then act on neuronal network function. Interestingly, human patients lacking the Shopper homolog SUOX develop neurological symptoms, including seizures. Given an enhanced expression of SUOX by oligodendrocytes, our findings might indicate that in both invertebrates and vertebrates more than one glial cell type may be involved in modulating neuronal activity. In Drosophila , ensheathing glia encase the neuropil but their function is not well understood. Here the authors show a surprising role of ensheathing glia in regulating glutamate homeostasis and locomotion which is controlled by the sulfite oxidase Shopper.