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Updated: Jun 21, 2025

Measuring Transcellular Interactions through Protein Aggregation in a Heterologous Cell System
Published on: May 22, 2020
Molecular and cellular mechanisms of teneurin signaling in synaptic partner matching
Chuanyun Xu1, Zhuoran Li1, Cheng Lyu2
1Department of Biology and Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA; Biology Graduate Program, Stanford University, Stanford, CA 94305, USA.
Abstract:
In developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionarily conserved teneurins are transmembrane proteins that instruct synaptic partner matching. However, how intracellular signaling pathways execute teneurins' functions is unclear. Here, we use in situ proximity labeling to obtain the intracellular interactome of a teneurin (Ten-m) in the Drosophila brain. Genetic interaction studies using quantitative partner matching assays in both olfactory receptor neurons (ORNs) and projection neurons (PNs) reveal a common pathway: Ten-m binds to and negatively regulates a RhoGAP, thus activating the Rac1 small GTPases to promote synaptic partner matching. Developmental analyses with single-axon resolution identify the cellular mechanism of synaptic partner matching: Ten-m signaling promotes local F-actin levels and stabilizes ORN axon branches that contact partner PN dendrites. Combining spatial proteomics and high-resolution phenotypic analyses, this study advanced our understanding of both cellular and molecular mechanisms of synaptic partner matching.
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