Sticks and stones, a conserved cell surface ligand for the Type IIa RPTP Lar, regulates neural circuit wiring in Drosophila

  1. Namrata Bali  Is a corresponding author
  2. Hyung-Kook (Peter) Lee
  3. Kai Zinn  Is a corresponding author
  1. California Institute of Technology, United States

Abstract

Type IIa receptor-like protein tyrosine phosphatases (RPTPs) are essential for neural development. They have cell adhesion molecule (CAM)-like extracellular domains that interact with cell-surface ligands and coreceptors. We identified the immunoglobulin superfamily CAM Sticks and Stones (Sns) as a new partner for the Drosophila Type IIa RPTP Lar. Lar and Sns bind to each other in embryos and in vitro, and the human Sns ortholog, Nephrin, binds to human Type IIa RPTPs. Genetic analysis shows that Lar and Sns function together to regulate larval neuromuscular junction development, axon guidance in the mushroom body (MB), and innervation of the optic lobe medulla by R7 photoreceptors. In the neuromuscular system, Lar and Sns are both required in motor neurons, and may function as coreceptors. In the MB and OL, however, the relevant Lar-Sns interactions are in trans (between neurons), so Sns functions as a Lar ligand in these systems.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files; Source Data files have been provided for Figure 4, Figure 4 - figure supplement 1 and 2, Figure 6 and Figure 6 - Figure supplement 1.

Article and author information

Author details

  1. Namrata Bali

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    For correspondence
    nbali@caltech.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7219-5439
  2. Hyung-Kook (Peter) Lee

    Division of Biology and Biological Engineering, California Institute of Technology, Pasadena, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. 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

Funding

National Institutes of Health (R37 NS028182)

  • Kai Zinn

National Institutes of Health (RO1 NS096509)

  • Kai Zinn

California Institute of Technology (Gordon Ross Postdoctoral Fellowship)

  • Namrata Bali

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

Publication history

  1. Preprint posted: November 5, 2020 (view preprint)
  2. Received: June 20, 2021
  3. Accepted: March 31, 2022
  4. Accepted Manuscript published: March 31, 2022 (version 1)
  5. Version of Record published: April 11, 2022 (version 2)

Copyright

© 2022, Bali 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. Namrata Bali
  2. Hyung-Kook (Peter) Lee
  3. Kai Zinn
(2022)
Sticks and stones, a conserved cell surface ligand for the Type IIa RPTP Lar, regulates neural circuit wiring in Drosophila
eLife 11:e71469.
https://doi.org/10.7554/eLife.71469
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