Brain-specific lipoprotein receptors interact with astrocyte derived apolipoprotein and mediate neuron-glia lipid shuttling

Lipid shuttling between neurons and glia contributes to the development, function, and stress responses of the nervous system. To understand how a neuron acquires its lipid supply from specific lipoproteins and their receptors, we perform combined genetic, transcriptome, and biochemical analyses in the developing Drosophila larval brain. Here we report, the astrocyte-derived secreted lipocalin Glial Lazarillo (GLaz), a homolog of human Apolipoprotein D (APOD), and its neuronal receptor, the brain-specific short isoforms of Drosophila lipophorin receptor 1 (LpR1-short), cooperatively mediate neuron-glia lipid shuttling and support dendrite morphogenesis. The isoform specificity of LpR1 defines its distribution, binding partners, and ability to support proper dendrite growth and synaptic connectivity. By demonstrating physical and functional interactions between GLaz/APOD and LpR1, we elucidate molecular pathways mediating lipid trafficking in the fly brain, and provide in vivo evidence indicating isoform-specific expression of lipoprotein receptors as a key mechanism for regulating cell-type specific lipid recruitment.


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For dendrite volume imaging and nile red staining experiments, we collected 10 to 20 samples for each genotype and condition. For FISH experiments, we collect !20 samples for each genotype and condition. These sample numbers are limited by the number of animals with desired genotypes from genetic crosses, and are similar to those reported in previous studies (Sheng C. et al., 2018, Yin J., et al., 2018.
No data were excluded.
We performed genetic analyses using different genetic reagents to ensure the reproducibility of the experimental findings. Experiments were performed and repeated by three different lab members. All findings can be reproduced.
The sample collection was randomized within each genotype and condition.
The group allocation in data collection can not be blinded due to the needs of the experiments. Specific genotypes and conditions are collected for data analyses. The data quantifications were performed blindly by co-authors without knowing the genotype and condition of the groups. Validation statements for the commercial antibodies are available on the manufactures websites.
Drosophila melanogaster is used in the study. for FISH, dendrite phenotype and lipid droplets study, both male and female are collected at the wandering third instar larval stage. For MALDI study, both male and female flies are collected at adult stage, 5