Stanford Advisors


All Publications


  • Endocytome profiling uncovers cell-surface protein dynamics underlying neuronal connectivity. Neuron McLaughlin, C. N., Ji, H., Dong, K. X., Xu, C., Wong, K. K., 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

    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.

    View details for DOI 10.1016/j.neuron.2026.01.027

    View details for PubMedID 41825443

  • Endosome-associated Rab GTPases control distinct aspects of neural circuit assembly. bioRxiv : the preprint server for biology Dong, K. X., Ji, H., Luginbuhl, D. J., Luo, L., McLaughlin, C. N. 2025

    Abstract

    Neural circuit assembly relies on the precise regulation of cell-surface receptors that mediate signaling and adhesion. Endocytosis controls receptor activity and availability by internalizing and routing proteins through two main pathways: recycling back to the cell-surface or delivery to lysosomes for degradation. Rab GTPases direct receptors into these distinct pathways, but their specific contributions to circuit formation remain opaque. Using clonal analyses with null alleles, we dissected the roles of Rab-mediated trafficking to early, late, and recycling endosomes across multiple stages of circuit assembly in vivo. Our approach revealed that Rab5 and Rab11 regulated extensive and largely distinct developmental events, highlighting the pivotal roles of early endosome sorting and recycling pathways in circuit assembly. We found that as neurons mature, both the spatial distribution and abundance of specific endocytic compartments change to reflect evolving trafficking demands. Our findings underscore how distinct post-endocytic trafficking fates are necessary to build neural circuits.

    View details for DOI 10.1101/2025.10.09.681358

    View details for PubMedID 41278817

    View details for PubMedCentralID PMC12632621

  • Endocytome profiling uncovers cell-surface protein dynamics underlying neuronal connectivity. bioRxiv : the preprint server for biology McLaughlin, C. N., Ji, H., Dong, K. X., Xu, C., Lam Wong, K. K., Li, Z., Luginbuhl, D. J., Xu, C., Lyu, C., Qin, W., Li, J., Udeshi, N. D., Carr, S. A., Ting, A. Y., Luo, L. 2025

    Abstract

    Endocytosis actively remodels the neuronal surface proteome to drive diverse cellular processes, yet its global extent and circuit-level consequences 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 olfactory receptor neuron (ORN) axons generated an endocytic atlas comprising over 1,100 proteins and revealed the extent to which the surface proteome is remodeled to meet distinct 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 wide-spread transcellular signaling and identified a growth factor secreted by neighboring neurons to direct ORN axon targeting via endocytic regulation of its receptor. Endocytome profiling thus provides unprecedented access to cell-surface proteome dynamics and offers a powerful platform for dissecting proteome remodeling across diverse cell types and contexts.

    View details for DOI 10.1101/2025.08.28.672852

    View details for PubMedID 40909753

    View details for PubMedCentralID PMC12407874