OSCR

Endocytome profiling uncovers cell-surface protein dynamics underlying neuronal connectivity.

Overview

Authors: Colleen N. McLaughlin1, Hui Ji1, Katherine X. Dong1, Chuanyun Xu1, Kenneth Kin Lam Wong1, Zhuoran Li1, David J. Luginbuhl1, Charles Xu2, Cheng Lyu1, Wei Qin3, Jiefu Li4, Namrata D. Udeshi2, Steven A. Carr2, Alice Y. Ting3, Liqun Luo1,5
ORCID iDs: Alice Y. Ting, Liqun Luo
  1. Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA
  2. Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
  3. Department of Genetics, Biology, and Chemistry, Chan Zuckerberg Biohub, Stanford University, Stanford, CA 94305, USA
  4. Janelia Research Campus, Howard Hughes Medical Institute, Ashburn, VA 20147, USA
  5. Lead contact
Institutions: Howard Hughes Medical Institute (United States); Stanford University (United States); Broad Institute (United States); Janelia Research Campus (United States)
Journal: Neuron, volume 114, issue 11, pages 1935-1950.e6
Dates: published online 12 March 2026; in print 3 June 2026
Type: Research article · Language: English
License: CC BY
Identifiers: DOI 10.1016/j.neuron.2026.01.027 · PMID 41825443 · PMCID PMC13055848 · OpenAlex W7135124598
Open access: hybrid, a free copy (OpenAlex)
Status: code on request
Categories: genetics / omics (modality), drosophila (organism), cellular / molecular (subfield)
Methods: Statistics, Evoked potentials
Keywords: Drosophila, Remodeling, Endosome, Proteomics, Olfactory Receptor Neuron, Axon Targeting, Proximity Labeling, Cell-surface Protein
MeSH: Drosophila Proteins*, Endocytosis*, Membrane Proteins*, Olfactory Receptor Neurons*, Animals, Axons, Drosophila, Drosophila melanogaster, Endosomes, Neurodevelopment, Proteome, Proteomics (* major topic)
Topic: Cellular transport and secretion (Cell Biology, Biochemistry, Genetics and Molecular Biology), according to OpenAlex
Funding: National Institutes of Health; Wu Tsai Neurosciences Institute, Stanford University; NIDCD NIH HHS (R01 DC005982, K99 DC021195); National Institute on Deafness and Other Communication Disorders (R01-DC005982, K99-DC021195); Howard Hughes Medical Institute
Citations: cited by 6 papers (Europe PMC); 97 references in the paper
Research resources: Chicken anti-GFP RRID:AB_10000240, Rabbit anti-dsRed RRID:AB_10013483, Rat anti-HA RRID:AB_10094468, Rabbit anti-HA RRID:AB_1549585, Gpat anti-HRP-594 RRID:AB_2338966, Mouse anti-mCherry RRID:AB_2536611, Mouse anti-V5 RRID:AB_2556564, Mouse anti-Rab7 RRID:AB_2722471, Rat anti-Ncad RRID:AB_528121, Mouse anti-Fas3 RRID:AB_528238, Mouse anti-Nrg RRID:AB_528402, Rabbit anti-Lamp1 RRID:AB_775973, Rabbit anti-Rab5 RRID:AB_882240, RRID:BDSC_30125, D. melanogaster: crb11A22 RRID:BDSC_3448, D. melanogaster: GH146-FLP RRID:BDSC_81291, D. melanogaster: tubP-GAL80 RRID:BDSC_9917, D. melanogaster: UAS-mCD8-GFP RRID:DGRC_108068, Fiji RRID:SCR_002285, Flymine RRID:SCR_002694, STRING RRID:SCR_005223, Revigo RRID:SCR_005825, Python RRID:SCR_008394, Illustrator RRID:SCR_010279, Zen Blue RRID:SCR_013672

Abstract

Endocytosis actively remodels the neuronal surface proteome to drive diverse cellular processes, yet its global extent and effects on neural circuit development have defied comprehensive interrogation. Here, we introduce endocytome profiling: a systematic, cell-type-specific approach for mapping cell-surface protein (CSP) dynamics in situ. Quantitative proteomic analysis of developing Drosophila olfactory receptor neuron (ORN) axons generated an endocytic atlas comprising over 1,000 proteins and revealed the extent to which the cell-surface proteome is remodeled to meet developmental demands. Targeted interrogation of a junctional CSP showed that its endosome-to-surface ratio is precisely balanced to enable developmental axon pruning while preserving mature axon integrity. Multi-omic integration uncovered widespread transcellular signaling and identified a growth factor secreted by neighboring neurons to direct ORN axon targeting via endocytic regulation of its receptor. Endocytome profiling provides unprecedented access to cell-surface proteome dynamics and offers a platform to dissect proteome-scale remodeling across diverse cell types and contexts.

Reproduced under the paper's license (CC BY), from the paper cited above.

Code

The paper says that its authors' code is available on request: it was not published with the paper, so there is nothing to verify.

The paper's code and data availability statement is in the Data section.

Tracing map

A tracing map links a paper to the code its authors published: this paper has none (its code is available on request), so it has no map.

Data

No dataset and no data link were found in the paper.

Data and code availability

The original mass spectra and the protein sequence databases used for searches have been deposited in the public proteomics repository MassIVE (http://massive.ucsd.edu) and are accessible at ftp:// proteomic data are provided in Table S2.

This paper does not report original code.

Any additional information required to reanalyze the data reported in this paper is available from the lead contact upon request.

Reproduced under the paper's license (CC BY), from the paper cited above.

Versions

The history of this record: each version stored by the harvester or made by a correction of its authors or of the maintainers of its code, and what changed in its facts. The texts of the paper (its abstract, its availability statements) are not part of it; versions that changed only those are not listed.

Version 1, 30 September 2026: the first record

Recorded: type, language, journal, volume, issue, pages, dates, 15 authors, 8 keywords, 12 MeSH terms, 5 funders, 97 references, 25 RRIDs.

Cite

This paper

McLaughlin, C. N., Ji, H., Dong, K. X., Xu, C., Wong, K. K. L., Li, Z., Luginbuhl, D. J., Xu, C., Lyu, C., Qin, W., Li, J., Udeshi, N. D., Carr, S. A., Ting, A. Y., & Luo, L. (2026). Endocytome profiling uncovers cell-surface protein dynamics underlying neuronal connectivity. Neuron, 114(11), 1935-1950.e6. https://doi.org/10.1016/j.neuron.2026.01.027

BibTeX

@article{mclaughlin2026endocytome,
author = {McLaughlin, Colleen N. and Ji, Hui and Dong, Katherine X. and Xu, Chuanyun and Wong, Kenneth Kin Lam and Li, Zhuoran and Luginbuhl, David J. and Xu, Charles and Lyu, Cheng and Qin, Wei and Li, Jiefu and Udeshi, Namrata D. and Carr, Steven A. and Ting, Alice Y. and Luo, Liqun},
title = {{Endocytome profiling uncovers cell-surface protein dynamics underlying neuronal connectivity}},
journal = {Neuron},
year = {2026},
month = mar,
volume = {114},
number = {11},
pages = {1935--1950.e6},
publisher = {Cell Press},
issn = {0896-6273},
doi = {10.1016/j.neuron.2026.01.027},
url = {https://doi.org/10.1016/j.neuron.2026.01.027},
pmid = {41825443},
pmcid = {PMC13055848}
}

RIS

TY - JOUR
AU - McLaughlin, Colleen N.
AU - Ji, Hui
AU - Dong, Katherine X.
AU - Xu, Chuanyun
AU - Wong, Kenneth Kin Lam
AU - Li, Zhuoran
AU - Luginbuhl, David J.
AU - Xu, Charles
AU - Lyu, Cheng
AU - Qin, Wei
AU - Li, Jiefu
AU - Udeshi, Namrata D.
AU - Carr, Steven A.
AU - Ting, Alice Y.
AU - Luo, Liqun
TI - Endocytome profiling uncovers cell-surface protein dynamics underlying neuronal connectivity
T2 - Neuron
J2 - Neuron
PY - 2026
DA - 2026/03/12
VL - 114
IS - 11
SP - 1935
EP - 1950.e6
SN - 0896-6273
PB - Cell Press
DO - 10.1016/j.neuron.2026.01.027
UR - https://doi.org/10.1016/j.neuron.2026.01.027
LA - en
ER -

CSL-JSON

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