All Publications
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Heterophilic interactions between cell-surface proteins Teneurin-m and Capricious drive dendrite segregation in the Drosophila olfactory circuit.
Current biology : CB
2026
Abstract
How dendrites of different neurons segregate into discrete spatial domains during neural circuit assembly is poorly understood. Here, using the Drosophila olfactory system, we found that heterophilic interactions between two cell-surface proteins, Teneurin-m (Ten-m) and Capricious (Caps), drive dendrite segregation. Ten-m and Caps are expressed in largely inverse patterns across projection neuron (PN) types when PNs are establishing their dendritic territories. Loss of Ten-m in Ten-m+ PNs causes their dendrites to invade Caps+ territories, whereas loss of Caps in Caps+ PNs causes dendrite invasion into Ten-m+ territories. Structure-guided mutations that abolish Ten-m-Caps binding disrupt dendrite segregation, whereas the same mutation on Ten-m preserves its homophilic attraction in a synaptic partner matching assay. These results support a model in which mutual repulsions between two inversely expressed cell-surface proteins drive dendrite segregation into discrete glomerular territories.
View details for DOI 10.1016/j.cub.2026.07.001
View details for PubMedID 42767218
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Endocytome profiling uncovers cell-surface protein dynamics underlying neuronal connectivity.
Neuron
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
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Endosome-associated Rab GTPases control distinct aspects of neural circuit assembly.
bioRxiv : the preprint server for biology
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