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Thrombospondin 1 accelerates synaptogenesis in hippocampal neurons through neuroligin 1

Abstract

In cultured rat hippocampal neurons, we found that thrombospondin 1 (TSP1) increased the speed of synapse formation in young neurons, but not the final density of synapses in mature neurons. TSP1 interacted with neuroligin 1 (NL1) and application of the NL1 extracellular domain blocked TSP1-induced synaptogenesis. Furthermore, knocking down endogenous NL1 inhibited TSP1's effect. Our results indicate that TSP1 accelerates the speed of synaptogenesis through NL1 in hippocampal neurons.

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Figure 1: TSP1 accelerates the speed of synaptogenesis, but does not increase the final density of synapses in mature neurons.
Figure 2: Neuroligin 1 extracellular domain blocks TSP1's synaptogenic effect and TSP1 interacts with neuroligins.
Figure 3: Neuroligin 1 knockdown suppresses TSP1-induced synaptogenesis.

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Acknowledgements

We thank W. Tung, C. He, P. Ieong and C. Sheng for technical assistance, A.M. Craig for YFP-NL1/2 and neurexin, P. Scheiffele for HA-NL1 and D. Comoletti for Flag–NL1-ECD cDNA constructs. This work was supported in part by grants from the Research Grants Council of Hong Kong (HKUST6429/06M, N_HKUST605/07, HKUST6/CRF/08, 663107 and AoE/B-15/01).

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J. Xu designed and conducted the experiments, analyzed the data and wrote the manuscript. N. X. contributed to some of the experiments. J. Xia designed the experiments, analyzed the data and wrote the manuscript.

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Correspondence to Jun Xia.

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Supplementary Figures 1–6 and Supplementary Methods (PDF 921 kb)

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Xu, J., Xiao, N. & Xia, J. Thrombospondin 1 accelerates synaptogenesis in hippocampal neurons through neuroligin 1. Nat Neurosci 13, 22–24 (2010). https://doi.org/10.1038/nn.2459

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