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UNC-6/netrin and its receptor UNC-5 locally exclude presynaptic components from dendrites

Nature volume 455, pages 669–673 (2008)Cite this article

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Abstract

Polarity is an essential feature of many cell types, including neurons that receive information from local inputs within their dendrites and propagate nerve impulses to distant targets through a single axon. It is generally believed that intrinsic structural differences between axons and dendrites dictate the polarized localization of axonal and dendritic proteins1. However, whether extracellular cues also instruct this process in vivo has not been explored. Here we show that the axon guidance cue UNC-6/netrin and its receptor UNC-5 act throughout development to exclude synaptic vesicle and active zone proteins from the dendrite of the Caenorhabditis elegans motor neuron DA9, which is proximal to a source of UNC-6/netrin. In unc-6/netrin and unc-5 loss-of-function mutants, presynaptic components mislocalize to the DA9 dendrite. In addition, ectopically expressed UNC-6/netrin, acting through UNC-5, is sufficient to exclude endogenous synapses from adjacent subcellular domains within the DA9 axon. Furthermore, this anti-synaptogenic activity is interchangeable with that of LIN-44/Wnt despite being transduced through different receptors, suggesting that extracellular cues such as netrin and Wnts not only guide axon navigation but also regulate the polarized accumulation of presynaptic components through local exclusion.

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Figure 1: GFP::RAB-3 is mislocalized to the dendrite in unc-5 and unc-6/netrin mutants.
Figure 2: UNC-5 acts cell autonomously in DA9 and is required throughout development.
Figure 3: UNC-6/netrin is sufficient to exclude GFP::RAB-3 locally and acts through UNC-5.
Figure 4: UNC-6/netrin and LIN-44/Wnt function interchangeably.

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Change history

  • 02 October 2008

    The AOP version of this paper contained inaccuracies in Figures 1 and 2. This was corrected for print on 2 October 2008.

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Acknowledgements

This work was supported by the W. M. Keck Foundation, the McKnight Endowment Fund, the Searle Scholar Award and the Howard Hughes Medical Institute. We thank the International Caenorhabditis Genetic Center and M. Chalfie for strains. We further thank M. Chalfie for sharing unpublished results on the silencing system. We also thank C. Gao and Y. Fu for technical assistance, and T. Clandinin, C. Bargmann, S. McConnell, and members of the Shen laboratory for comments on the manuscript.

Author Contributions V.Y.P., M.P.K. and K.S. designed the experiments; V.Y.P. performed the experiments and data analysis; V.Y.P., M.P.K. and K.S. wrote the paper.

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Authors and Affiliations

  1. Neuroscience Program, Stanford University School of Medicine, 300 Pasteur Drive, California 94305, USA ,

    Vivian Y. Poon, Matthew P. Klassen & Kang Shen

  2. Department of Biology, Howard Hughes Medical Institute, Stanford University, 385 Serra Mall, California 94305, USA,

    Kang Shen

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Correspondence to Kang Shen.

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Poon, V., Klassen, M. & Shen, K. UNC-6/netrin and its receptor UNC-5 locally exclude presynaptic components from dendrites. Nature 455, 669–673 (2008). https://doi.org/10.1038/nature07291

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