Transsynaptic interactions between IgSF proteins DIP-α and Dpr10 are required for motor neuron targeting specificity

  1. James Ashley
  2. Violet Sorrentino
  3. Meike Lobb-Rabe
  4. Sonal Nagarkar-Jaiswal
  5. Liming Tan
  6. Shuwa Xu
  7. Qi Xiao
  8. Kai Zinn  Is a corresponding author
  9. Robert A Carrillo  Is a corresponding author
  1. University of Chicago, United States
  2. Baylor College of Medicine, United States
  3. University of California, Los Angeles, United States
  4. California Institute of Technology, United States

Abstract

The Drosophila larval neuromuscular system provides an ideal context in which to study synaptic partner choice, because it contains a small number of pre- and postsynaptic cells connected in an invariant pattern. The discovery of interactions between two subfamilies of IgSF cell surface proteins, the Dprs and the DIPs, provided new candidates for cellular labels controlling synaptic specificity. Here we show that DIP-α is expressed by two identified motor neurons, while its binding partner Dpr10 is expressed by postsynaptic muscle targets. Removal of either DIP-α or Dpr10 results in loss of specific axonal branches and NMJs formed by one motor neuron, MNISN-1s, while other branches of the MNISN-1s axon develop normally. The temporal and spatial expression pattern of dpr10 correlates with muscle innervation by MNISN-1s during embryonic development. We propose a model whereby DIP-α and Dpr10 on opposing synaptic partners interact with each other to generate proper motor neuron connectivity.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. James Ashley

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Violet Sorrentino

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Meike Lobb-Rabe

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Sonal Nagarkar-Jaiswal

    Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Liming Tan

    Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Shuwa Xu

    Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Qi Xiao

    Department of Biological Chemistry, University of California, Los Angeles, Los Angeles, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Kai Zinn

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    For correspondence
    zinnk@caltech.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6706-5605
  9. Robert A Carrillo

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    For correspondence
    robertcarrillo@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-2067-9861

Funding

National Institute of Neurological Disorders and Stroke (K01 NS102342)

  • Robert A Carrillo

National Institute of Neurological Disorders and Stroke (R01 NS096509)

  • Kai Zinn

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

Reviewing Editor

  1. K VijayRaghavan, National Centre for Biological Sciences, Tata Institute of Fundamental Research, India

Version history

  1. Received: October 9, 2018
  2. Accepted: January 31, 2019
  3. Accepted Manuscript published: February 4, 2019 (version 1)
  4. Version of Record published: February 26, 2019 (version 2)

Copyright

© 2019, Ashley 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

  • 1,976
    views
  • 302
    downloads
  • 42
    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. James Ashley
  2. Violet Sorrentino
  3. Meike Lobb-Rabe
  4. Sonal Nagarkar-Jaiswal
  5. Liming Tan
  6. Shuwa Xu
  7. Qi Xiao
  8. Kai Zinn
  9. Robert A Carrillo
(2019)
Transsynaptic interactions between IgSF proteins DIP-α and Dpr10 are required for motor neuron targeting specificity
eLife 8:e42690.
https://doi.org/10.7554/eLife.42690

Share this article

https://doi.org/10.7554/eLife.42690

Further reading

    1. Cell Biology
    2. Neuroscience
    Toshiharu Ichinose, Shu Kondo ... Hiromu Tanimoto
    Research Article

    Multicellular organisms are composed of specialized cell types with distinct proteomes. While recent advances in single-cell transcriptome analyses have revealed differential expression of mRNAs, cellular diversity in translational profiles remains underinvestigated. By performing RNA-seq and Ribo-seq in genetically defined cells in the Drosophila brain, we here revealed substantial post-transcriptional regulations that augment the cell-type distinctions at the level of protein expression. Specifically, we found that translational efficiency of proteins fundamental to neuronal functions, such as ion channels and neurotransmitter receptors, was maintained low in glia, leading to their preferential translation in neurons. Notably, distribution of ribosome footprints on these mRNAs exhibited a remarkable bias toward the 5′ leaders in glia. Using transgenic reporter strains, we provide evidence that the small upstream open-reading frames in the 5’ leader confer selective translational suppression in glia. Overall, these findings underscore the profound impact of translational regulation in shaping the proteomics for cell-type distinction and provide new insights into the molecular mechanisms driving cell-type diversity.

    1. Cancer Biology
    2. Cell Biology
    Camille Dantzer, Justine Vaché ... Violaine Moreau
    Research Article

    Immune checkpoint inhibitors have produced encouraging results in cancer patients. However, the majority of ß-catenin-mutated tumors have been described as lacking immune infiltrates and resistant to immunotherapy. The mechanisms by which oncogenic ß-catenin affects immune surveillance remain unclear. Herein, we highlighted the involvement of ß-catenin in the regulation of the exosomal pathway and, by extension, in immune/cancer cell communication in hepatocellular carcinoma (HCC). We showed that mutated ß-catenin represses expression of SDC4 and RAB27A, two main actors in exosome biogenesis, in both liver cancer cell lines and HCC patient samples. Using nanoparticle tracking analysis and live-cell imaging, we further demonstrated that activated ß-catenin represses exosome release. Then, we demonstrated in 3D spheroid models that activation of β-catenin promotes a decrease in immune cell infiltration through a defect in exosome secretion. Taken together, our results provide the first evidence that oncogenic ß-catenin plays a key role in exosome biogenesis. Our study gives new insight into the impact of ß-catenin mutations on tumor microenvironment remodeling, which could lead to the development of new strategies to enhance immunotherapeutic response.