A multi-protein receptor-ligand complex underlies combinatorial dendrite guidance choices in C. elegans

  1. Wei Zou
  2. Ao Shen
  3. Xintong Dong
  4. Madina Tugizova
  5. Yang K Xiang
  6. Kang Shen  Is a corresponding author
  1. Howard Hughes Medical Institute, Stanford University, United States
  2. University of California, Davis, United States

Abstract

Ligand receptor interactions instruct axon guidance during development. How dendrites are guided to specific targets is less understood. The C. elegans PVD sensory neuron innervates muscle-skin interface with its elaborate dendritic branches. Here, we found that LECT-2, the ortholog of leukocyte cell-derived chemotaxin-2 (LECT2), is secreted from the muscles and required for muscle innervation by PVD. Mosaic analyses showed that LECT-2 acted locally to guide the growth of terminal branches. Ectopic expression of LECT-2 from seam cells is sufficient to redirect the PVD dendrites onto seam cells. LECT-2 functions in a multi-protein receptor-ligand complex that also contains two transmembrane ligands on the skin, SAX-7/L1CAM and MNR-1, and the neuronal transmembrane receptor DMA-1. LECT-2 greatly enhances the binding between SAX-7, MNR-1 and DMA-1. The activation of DMA-1 strictly requires all three ligands, which establishes a combinatorial code to precisely target and pattern dendritic arbors.

Article and author information

Author details

  1. Wei Zou

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  2. Ao Shen

    Department of Pharmacology, University of California, Davis, Davis, United States
    Competing interests
    No competing interests declared.
  3. Xintong Dong

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  4. Madina Tugizova

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  5. Yang K Xiang

    Department of Pharmacology, University of California, Davis, Davis, United States
    Competing interests
    No competing interests declared.
  6. Kang Shen

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    For correspondence
    kangshen@stanford.edu
    Competing interests
    Kang Shen, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4059-8249

Funding

Howard Hughes Medical Institute

  • Wei Zou
  • Xintong Dong
  • Madina Tugizova
  • Kang Shen

National Institute of Neurological Disorders and Stroke (1R01NS082208)

  • Wei Zou
  • Xintong Dong
  • Madina Tugizova
  • Kang Shen

National Heart, Lung, and Blood Institute (R01HL127764-01)

  • Ao Shen
  • Yang K Xiang

American Heart Association

  • Ao Shen

NIH Office of Research Infrastructure Programs (P40 OD010440)

  • Kang Shen

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Graeme W Davis, University of California, San Francisco, United States

Version history

  1. Received: May 31, 2016
  2. Accepted: October 3, 2016
  3. Accepted Manuscript published: October 5, 2016 (version 1)
  4. Version of Record published: October 25, 2016 (version 2)

Copyright

© 2016, Zou et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Wei Zou
  2. Ao Shen
  3. Xintong Dong
  4. Madina Tugizova
  5. Yang K Xiang
  6. Kang Shen
(2016)
A multi-protein receptor-ligand complex underlies combinatorial dendrite guidance choices in C. elegans
eLife 5:e18345.
https://doi.org/10.7554/eLife.18345

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https://doi.org/10.7554/eLife.18345

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