Molecular and Cellular Mechanisms of Teneurin Signaling in Synaptic Partner Matching

Download This Paper Open PDF in Browser Add Paper to My Library Share: Permalink Using these links will ensure access to this page indefinitely Copy URL Molecular and Cellular Mechanisms of Teneurin Signaling in Synaptic Partner Matching Cell 57 Pages Posted: 21 Feb 2024 Publication Status: Under Review See all articles by Chuanyun XuChuanyun XuStanford UniversityZhuoran LiStanford UniversityCheng LyuStanford UniversityYixin HuStanford UniversityColleen McLaughlinStanford UniversityKenneth Kim Lam WongStanford UniversityQijing XieStanford UniversityDavid J. LuginbuhlStanford University - Department of BiologyHongjie LiStanford UniversityNamrata UdeshiMassachusetts Institute of Technology and Harvard University - Proteomics PlatformTanya SvinkinaMassachusetts Institute of Technology and Harvard University - Broad InstituteD. R. ManiMassachusetts Institute of Technology and Harvard University - Broad InstituteShuo HanStanford UniversityTongchao LiStanford UniversityYang LiStanford UniversityRicardo GuajardoStanford UniversityAlice TingStanford University - Department of Genetics; Stanford University - Department of BiologySteven A. CarrMassachusetts Institute of Technology and Harvard University - Proteomics PlatformJiefu LiStanford UniversityLiqun LuoStanford University - Department of Biology; Stanford University - Department of Bioengineering; Stanford University - Department of Applied Physics; Stanford University - Chan Zuckerberg Biohub More... Abstract In developing brains, axons exhibit remarkable precision in selecting synaptic partners among many non-partner cells. Evolutionally conserved teneurins were the first identified transmembrane proteins that instruct synaptic partner matching. However, how intracellular signaling pathways execute teneurin’s functions is unclear. Here, we use in situ proximity labeling to obtain the intracellular interactome of 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. Keywords: Neural circuit assembly, wiring specificity, synaptic partner matching, axon, dendrite, synapse, olfactory system, olfactory receptor neuron, projection neuron, glomeruli, teneurin, type-II transmembrane protein, homophilic attraction, intracellular signaling, RhoGAP, Rho GTPases, Rac1, F-actin, branch stabilization, spatial proteomics, proximity labeling, sparse labeling, genetic interaction Suggested Citation: Suggested Citation Xu, Chuanyun and Li, Zhuoran and Lyu, Cheng and Hu, Yixin and McLaughlin, Colleen and Wong, Kenneth Kim Lam and Xie, Qijing and Luginbuhl, David J. and Li, Hongjie and Udeshi, Namrata and Svinkina, Tanya and Mani, D. R. and Han, Shuo and Li, Tongchao and Li, Yang and Guajardo, Ricardo and Ting, Alice and Carr, Steven A. and Li, Jiefu and Luo, Liqun, Molecular and Cellular Mechanisms of Teneurin Signaling in Synaptic Partner Matching. Available at SSRN: https://ssrn.com/abstract=4733246 This version of the paper has not been formally peer reviewed. Chuanyun Xu Stanford University ( email ) Zhuoran Li Stanford University ( email ) Stanford, CA 94305United States Cheng Lyu Stanford University ( email ) Stanford, CA 94305United States Yixin Hu Stanford University ( email ) Stanford, CA 94305United States Colleen McLaughlin Stanford University ( email ) Stanford, CA 94305United States Kenneth Kim Lam Wong Stanford University ( email ) Stanford, CA 94305United States Qijing Xie Stanford University ( email ) Stanford, CA 94305United States David J. Luginbuhl Stanford University - Department of Biology ( email ) Gilbert Building, Rm 109371 Serra MallStanford, CA 94305United States Hongjie Li Stanford University ( email ) Stanford, CA 94305United States Namrata Udeshi Massachusetts Institute of Technology and Harvard University - Proteomics Platform ( email ) Tanya Svinkina Massachusetts Institute of Technology and Harvard University - Broad Institute ( email ) 415 Main StreetCambridge, MA 02142United States D. R. Mani Massachusetts Institute of Technology and Harvard University - Broad Institute ( email ) Shuo Han Stanford University ( email ) Stanford, CA 94305United States Tongchao Li Stanford University ( email ) Stanford, CA 94305United States Yang Li Stanford University ( email ) Stanford, CA 94305United States Ricardo Guajardo Stanford University ( email ) Stanford, CA 94305United States Alice Ting Stanford University - Department of Genetics ( email ) Stanford, CA 94305United States Stanford University - Department of Biology ( email ) Gilbert Building, Rm 109371 Serra MallStanford, CA 94305United States Steven A. Carr Massachusetts Institute of Technology and Harvard University - Proteomics Platform ( email ) Jiefu Li Stanford University ( email ) Liqun Luo (Contact Author) Stanford University - Department of Biology ( email ) Stanford, CAUnited States Stanford University - Department of Bioengineering ( email ) Stanford, CA 94305United States Stanford University - Department of Applied Physics ( email ) CAUnited States Stanford University - Chan Zuckerberg Biohub 499 Illinois StreetSan Francisco, CA 94158United States Download This Paper Open PDF in Browser Please enable JavaScript to view the comments powered by Disqus. 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