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.

Reviewing Editor

  1. Hugo J Bellen, Howard Hughes Medical Institute, Baylor College of Medicine, United States

Publication history

  1. Received: August 20, 2015
  2. Accepted: February 26, 2016
  3. Accepted Manuscript published: March 14, 2016 (version 1)
  4. Version of Record published: March 21, 2016 (version 2)

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.

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  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

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