@article{2019804d84714b6196212e9d40076771,
title = "Neuronal activity induces glucosylceramide that is secreted via exosomes for lysosomal degradation in glia",
abstract = "Recessive variants in GBA1 cause Gaucher disease, a prevalent form of lysosome storage disease. GBA1 encodes a lysosomal enzyme that hydrolyzes glucosylceramide (GlcCer) into glucose and ceramide. Its loss causes lysosomal dysfunction and increased levels of GlcCer. We generated a null allele of the Drosophila ortholog Gba1b by inserting the Gal4 using CRISPR-Cas9. Here, we show that Gba1b is expressed in glia but not in neurons. Glial-specific knockdown recapitulates the defects found in Gba1b mutants, and these can be rescued by glial expression of human GBA1. We show that GlcCer is synthesized upon neuronal activity, and it is transported from neurons to glia through exosomes. Furthermore, we found that glial TGF-β/BMP induces the transfer of GlcCer from neurons to glia and that the White protein, an ABCG transporter, promotes GlcCer trafficking to glial lysosomes for degradation.",
author = "Liping Wang and Guang Lin and Zhongyuan Zuo and Yarong Li and Byeon, {Seul Kee} and Akhilesh Pandey and Bellen, {Hugo J.}",
note = "Funding Information: We thank J. Shulman, S. Yamamoto, M. Wang, C. Wilson, H. Zoghbi, K. Kinghorn, and O. Kanca for insightful comments. We thank L. Pallanck, K. Kinghorn, K. Wharton, and P. Garrity for sharing fly stocks. We thank P. Marcogliese for cloning pUASTattb_GBA1 plasmid and M. Ma for cloning pUASTattb_white-HA plasmid. We thank H. Pan for injections to create transgenic flies. We thank the Bloomington Drosophila Stock Center and Vienna Drosophila Resource Center for providing stocks and reagents. We acknowledge support from HHMI, the Jan and Dan Duncan Neurological Research Institute, and the Huffington Foundation. This work was supported by the Huffington Foundation. Publisher Copyright: {\textcopyright} 2022 The Authors, some rights reserved",
year = "2022",
month = jul,
doi = "10.1126/sciadv.abn3326",
language = "English (US)",
volume = "8",
journal = "Science advances",
issn = "2375-2548",
publisher = "American Association for the Advancement of Science",
number = "28",
}