UMMS Affiliation

Department of Neurobiology

Publication Date

2018-10-30

Document Type

Article

Disciplines

Amino Acids, Peptides, and Proteins | Lipids | Neuroscience and Neurobiology | Nucleic Acids, Nucleotides, and Nucleosides

Abstract

Activity-dependent modifications strongly influence neural development. However, molecular programs underlying their context and circuit-specific effects are not well understood. To study global transcriptional changes associated with chronic elevation of synaptic activity, we performed cell-type-specific transcriptome profiling of Drosophila ventral lateral neurons (LNvs) in the developing visual circuit and identified activity-modified transcripts that are enriched in neuron morphogenesis, circadian regulation, and lipid metabolism and trafficking. Using bioinformatics and genetic analyses, we validated activity-induced isoform-specific upregulation of Drosophila lipophorin receptors LpR1 and LpR2, the homologs of mammalian low-density lipoprotein receptor (LDLR) family proteins. Furthermore, our morphological and physiological studies uncovered critical functions of neuronal lipophorin receptors (LpRs) in maintaining the structural and functional integrities in neurons challenged by chronic elevations of activity. Together, our findings identify LpRs as molecular targets for activity-dependent transcriptional regulation and reveal the functional significance of cell-type-specific regulation of neuronal lipid uptake in experience-dependent plasticity and adaptive responses.

Keywords

RNA-seq analysis, activity-dependent transcriptional regulation, dendrite morphogenesis, lipid homeostasis, lipid uptake, lipoprotein receptor, neural development, neuronal adaptation, structural plasticity, transcriptome profiling

Rights and Permissions

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI of Published Version

10.1016/j.celrep.2018.10.016

Source

Cell Rep. 2018 Oct 30;25(5):1181-1192.e4. doi: 10.1016/j.celrep.2018.10.016. Link to article on publisher's site

Journal/Book/Conference Title

Cell reports

Related Resources

Link to Article in PubMed

PubMed ID

30380410

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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