Transcriptional Regulation of Lipophorin Receptors Supports Neuronal Adaptation to Chronic Elevations of Activity

Cell Rep. 2018 Oct 30;25(5):1181-1192.e4. doi: 10.1016/j.celrep.2018.10.016.


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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Adaptation, Physiological / genetics*
  • Animals
  • Dendrites / metabolism
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics*
  • Gene Expression Regulation*
  • Morphogenesis
  • Neurons / physiology*
  • RNA Interference
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Cytoplasmic and Nuclear / genetics*
  • Receptors, Cytoplasmic and Nuclear / metabolism
  • Transcription, Genetic*
  • Transcriptome / genetics
  • Up-Regulation / genetics


  • Drosophila Proteins
  • Lpr1 protein, Drosophila
  • Lpr2 protein, Drosophila
  • RNA, Messenger
  • Receptors, Cytoplasmic and Nuclear