Journal article
Astrocyte growth is driven by the Tre1/S1pr1 phospholipid-binding G protein-coupled receptor
Neuron (Cambridge, Mass.), Vol.112(1), pp.93-112.e10
01/03/2024
DOI: 10.1016/j.neuron.2023.11.008
PMCID: PMC11073822
PMID: 38096817
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.
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•The GPCR Tre1 and LPPs Wun/Wun2 promote astrocyte process outgrowth in Drosophila•Astrocytes compete for growth-promoting phospholipids (PLs) in the CNS•LPPs Wun/Wun2 act locally to regulate PL levels and process outgrowth through Tre1•Vertebrate S1pr1 regulates astrocyte growth through modulation of process dynamics
Chen et al. show that the lipid-binding GPCR Tre1/S1pr1 promotes astrocyte morphological growth in Drosophila and zebrafish. Astrocytes compete for local phospholipids, which are processed by the LPPs Wun/Wun2 to promote process outgrowth via Tre1, thereby enabling astrocyte control of behavior.
Details
- Title: Subtitle
- Astrocyte growth is driven by the Tre1/S1pr1 phospholipid-binding G protein-coupled receptor
- Creators
- Jiakun Chen - Oregon Health & Science UniversityTobias Stork - Oregon Health & Science UniversityYunsik Kang - Oregon Health & Science UniversityKatherine A.M. Nardone - New York University School of MedicineFranziska Auer - New York UniversityRyan J. Farrell - NYU Langone HealthTaylor R. Jay - Oregon Health & Science UniversityDongeun Heo - Oregon Health & Science UniversityAmy Sheehan - Oregon Health & Science UniversityCameron Paton - Oregon Health & Science UniversityKatherine I. Nagel - NYU Langone HealthDavid Schoppik - New York UniversityKelly R. Monk - Oregon Health & Science UniversityMarc R. Freeman - Oregon Health & Science University
- Resource Type
- Journal article
- Publication Details
- Neuron (Cambridge, Mass.), Vol.112(1), pp.93-112.e10
- DOI
- 10.1016/j.neuron.2023.11.008
- PMID
- 38096817
- PMCID
- PMC11073822
- NLM abbreviation
- Neuron
- ISSN
- 0896-6273
- eISSN
- 1097-4199
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 01/03/2024
- Academic Unit
- Iowa Neuroscience Institute; Neuroscience and Pharmacology
- Record Identifier
- 9985112882502771
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