Precise regulation of the guidance receptor DMA-1 by KPC-1/Furin instructs dendritic branching decisions

  1. Xintong Dong
  2. Hui Chiu
  3. Yeonhee Jenny Park
  4. Wei Zou
  5. Yan Zou
  6. Engin Özkan
  7. Chieh Chang
  8. Kang Shen  Is a corresponding author
  1. Howard Hughes Medical Institute, Stanford University, United States
  2. California Institute of Technology, United States
  3. University of Chicago, United States
  4. Shanghai Tech University, China
  5. University of Illinois at Chicago, United States

Abstract

Extracellular adhesion molecules and their neuronal receptors guide the growth and branching of axons and dendrites. Growth cones are attracted to intermediate targets, but they must switch their response upon arrival so that they can move away and complete the next stage of growth. Here, we show that KPC-1, a C. elegans Furin homolog, regulates the level of the branching receptor DMA-1 on dendrites by targeting it to late endosomes. In kpc-1 mutants, the level of DMA-1 is abnormally high on dendrites, resulting in trapping of dendrites at locations where a high level of the cognate ligand, the adhesion molecule SAX-7/L1, is present. The misregulation of DMA-1 also causes dendritic self-avoidance defects. Thus, precise regulation of guidance receptors creates flexibility of responses to guidance signals and is critical for neuronal morphogenesis.

Article and author information

Author details

  1. Xintong Dong

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

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    No competing interests declared.
  3. Yeonhee Jenny Park

    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States
    Competing interests
    No competing interests declared.
  4. Wei Zou

    Department of Biology, Howard Hughes Medical Institute, Stanford University, Stanford, United States
    Competing interests
    No competing interests declared.
  5. Yan Zou

    School of Life Science, Shanghai Tech University, Shanghai, China
    Competing interests
    No competing interests declared.
  6. Engin Özkan

    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States
    Competing interests
    No competing interests declared.
  7. Chieh Chang

    Department of Biological Sciences, University of Illinois at Chicago, Chicago, United States
    Competing interests
    No competing interests declared.
  8. 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.

Copyright

© 2016, Dong 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.

Metrics

  • 2,605
    views
  • 502
    downloads
  • 35
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Xintong Dong
  2. Hui Chiu
  3. Yeonhee Jenny Park
  4. Wei Zou
  5. Yan Zou
  6. Engin Özkan
  7. Chieh Chang
  8. Kang Shen
(2016)
Precise regulation of the guidance receptor DMA-1 by KPC-1/Furin instructs dendritic branching decisions
eLife 5:e11008.
https://doi.org/10.7554/eLife.11008

Share this article

https://doi.org/10.7554/eLife.11008

Further reading

    1. Developmental Biology
    Thomas A Bos, Elizaveta Polyakova ... Monique RM Jongbloed
    Research Article Updated

    Human autonomic neuronal cell models are emerging as tools for modeling diseases such as cardiac arrhythmias. In this systematic review, we compared 33 articles applying 14 different protocols to generate sympathetic neurons and 3 different procedures to produce parasympathetic neurons. All methods involved the differentiation of human pluripotent stem cells, and none employed permanent or reversible cell immortalization. Almost all protocols were reproduced in multiple pluripotent stem cell lines, and over half showed evidence of neural firing capacity. Common limitations in the field are a lack of three-dimensional models and models that include multiple cell types. Sympathetic neuron differentiation protocols largely mirrored embryonic development, with the notable absence of migration, axon extension, and target-specificity cues. Parasympathetic neuron differentiation protocols may be improved by including several embryonic cues promoting cell survival, cell maturation, or ion channel expression. Moreover, additional markers to define parasympathetic neurons in vitro may support the validity of these protocols. Nonetheless, four sympathetic neuron differentiation protocols and one parasympathetic neuron differentiation protocol reported more than two-thirds of cells expressing autonomic neuron markers. Altogether, these protocols promise to open new research avenues of human autonomic neuron development and disease modeling.

    1. Cell Biology
    2. Developmental Biology
    Sarah Y Coomson, Salil A Lachke
    Insight

    A study in mice reveals key interactions between proteins involved in fibroblast growth factor signaling and how they contribute to distinct stages of eye lens development.