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

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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.

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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.

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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.

"This ORCID iD identifies the author of this article:" 0000-0002-7219-5439
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.
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.

"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.

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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.