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Related Experiment Video

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Differential Labeling of Cell-surface and Internalized Proteins after Antibody Feeding of Live Cultured Neurons
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Endocytome profiling uncovers cell-surface protein dynamics underlying neuronal connectivity.

Colleen N McLaughlin1, Hui Ji1, Katherine X Dong1

  • 1Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA.

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|March 13, 2026
PubMed
Summary

We developed endocytome profiling to map cell-surface protein dynamics during neural development. This method revealed how endocytosis shapes neuronal connections and identified signaling pathways critical for axon targeting.

Keywords:
Drosophilaaxon targetingcell-surface proteinendosomeolfactory receptor neuronproteomicsproximity labelingremodeling

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Area of Science:

  • Neuroscience
  • Cell Biology
  • Proteomics

Background:

  • Endocytosis is crucial for neuronal function, remodeling the cell surface proteome.
  • The global impact of endocytosis on neural circuit development remains poorly understood.

Purpose of the Study:

  • To systematically map cell-surface protein dynamics during neural development using a cell-type-specific approach.
  • To investigate the role of endocytosis in axon pruning and targeting.

Main Methods:

  • Developed endocytome profiling, a quantitative proteomic method.
  • Analyzed developing Drosophila olfactory receptor neuron (ORN) axons.
  • Integrated multi-omic data.

Main Results:

  • Generated an endocytic atlas of over 1,000 proteins.
  • Demonstrated precise endosome-to-surface protein ratio regulation for axon pruning and integrity.
  • Identified transcellular signaling pathways regulating axon targeting via receptor endocytosis.

Conclusions:

  • Endocytome profiling offers unprecedented access to cell-surface proteome dynamics.
  • This approach provides a platform for dissecting proteome-scale remodeling in various cell types.
  • Endocytosis plays a critical role in orchestrating neural circuit development.