Molecular basis of synaptic specificity by immunoglobulin superfamily receptors in Drosophila
- University of Chicago, United States
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).
Article and author information
Author details
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
- Axel T Brunger, Stanford University, United States
Version history
- Received: August 11, 2018
- Accepted: January 22, 2019
- Accepted Manuscript published: January 28, 2019 (version 1)
- Accepted Manuscript updated: January 31, 2019 (version 2)
- 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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Molecular basis of synaptic specificity by immunoglobulin superfamily receptors in Drosophila
eLife 8:e41028.
https://doi.org/10.7554/eLife.41028
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