1. Neuroscience
  2. Structural Biology and Molecular Biophysics
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Molecular basis of synaptic specificity by immunoglobulin superfamily receptors in Drosophila

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Cite this article as: eLife 2019;8:e41028 doi: 10.7554/eLife.41028

Abstract

In stereotyped neuronal networks, synaptic connectivity is dictated by cell surface proteins, which assign unique identities to neurons, and physically mediate axon guidance and synapse targeting. We recently identified two groups of immunoglobulin superfamily proteins in Drosophila, Dprs and DIPs, as strong candidates for synapse targeting functions. Here, we uncover the molecular basis of specificity in Dpr–DIP mediated cellular adhesions and neuronal connectivity. First, we present five crystal structures of Dpr–DIP and DIP–DIP complexes, highlighting the evolutionary and structural origins of diversification in Dpr and DIP proteins and their interactions. We further show that structures can be used to rationally engineer receptors with novel specificities or modified affinities, which can be used to study specific circuits that require Dpr–DIP interactions to help establish connectivity. We investigate one pair, engineered Dpr10 and DIP-α, for function in the neuromuscular circuit in flies, and reveal roles for homophilic and heterophilic binding in wiring.

Data availability

Structural models and diffraction data have been deposited in PDB (accession numbers: 6NRQ, 6NRR, 6NRX, 6NRW, and 6NS1).

The following data sets were generated

Article and author information

Author details

  1. Shouqiang Cheng

    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. 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.
  3. Justyna D Kurleto

    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. 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.
  5. Yeonhee Jenny Park

    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Robert A Carrillo

    Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, United States
    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
  7. Engin Özkan

    Department of Biochemistry and Molecular Biology, University of Chicago, Chicago, United States
    For correspondence
    eozkan@uchicago.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-0263-6729

Funding

National Institute of Neurological Disorders and Stroke (R01 NS097161)

  • Engin Özkan

Esther A. and Joseph Klingenstein Fund

  • Engin Özkan

National Institute of Neurological Disorders and Stroke (K01 NS102342)

  • Robert A Carrillo

Alfred P. Sloan Foundation

  • Engin Özkan

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

Reviewing Editor

  1. Axel T Brunger, Stanford University, United States

Publication history

  1. Received: August 11, 2018
  2. Accepted: January 22, 2019
  3. Accepted Manuscript published: January 28, 2019 (version 1)
  4. Accepted Manuscript updated: January 31, 2019 (version 2)
  5. Version of Record published: February 13, 2019 (version 3)

Copyright

© 2019, Cheng 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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