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Article ; Online: Astrocyte growth is driven by the Tre1/S1pr1 phospholipid-binding G protein-coupled receptor.

Chen, Jiakun / Stork, Tobias / Kang, Yunsik / Nardone, Katherine A M / Auer, Franziska / Farrell, Ryan J / Jay, Taylor R / Heo, Dongeun / Sheehan, Amy / Paton, Cameron / Nagel, Katherine I / Schoppik, David / Monk, Kelly R / Freeman, Marc R

Neuron

2023  Volume 112, Issue 1, Page(s) 93–112.e10

Abstract: Astrocytes play crucial roles in regulating neural circuit function by forming a dense network of synapse-associated membrane specializations, but signaling pathways regulating astrocyte morphogenesis remain poorly defined. Here, we show the Drosophila ... ...

Abstract Astrocytes play crucial roles in regulating neural circuit function by forming a dense network of synapse-associated membrane specializations, but signaling pathways regulating astrocyte morphogenesis remain poorly defined. Here, we show the Drosophila lipid-binding G protein-coupled receptor (GPCR) Tre1 is required for astrocytes to establish their intricate morphology in vivo. The lipid phosphate phosphatases Wunen/Wunen2 also regulate astrocyte morphology and, via Tre1, mediate astrocyte-astrocyte competition for growth-promoting lipids. Loss of s1pr1, the functional analog of Tre1 in zebrafish, disrupts astrocyte process elaboration, and live imaging and pharmacology demonstrate that S1pr1 balances proper astrocyte process extension/retraction dynamics during growth. Loss of Tre1 in flies or S1pr1 in zebrafish results in defects in simple assays of motor behavior. Tre1 and S1pr1 are thus potent evolutionarily conserved regulators of the elaboration of astrocyte morphological complexity and, ultimately, astrocyte control of behavior.
MeSH term(s) Animals ; Astrocytes/metabolism ; Drosophila/metabolism ; Drosophila Proteins/metabolism ; Phospholipids/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Sphingosine-1-Phosphate Receptors/metabolism ; Zebrafish
Chemical Substances Drosophila Proteins ; Phospholipids ; Receptors, G-Protein-Coupled ; Sphingosine-1-Phosphate Receptors ; Tre1 protein, Drosophila
Language English
Publishing date 2023-12-13
Publishing country United States
Document type Journal Article
ZDB-ID 808167-0
ISSN 1097-4199 ; 0896-6273
ISSN (online) 1097-4199
ISSN 0896-6273
DOI 10.1016/j.neuron.2023.11.008
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