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Published March 31, 2022 | Supplemental Material + Submitted + Published
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Sticks and Stones, a conserved cell surface ligand for the Type IIa RPTP Lar, regulates neural circuit wiring in Drosophila


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 (OL) 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.

Additional Information

© 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. Preprinted: 05 November 2020; Received: 20 June 2021; Accepted: 31 March 2022; Published: 31 March 2022. We thank Michael Anaya for discussions about in vitro binding assays, Yelena Smirnova and Annie Lam for technical assistance, Violana Nesterova for figure preparation, and Kaushiki Menon and Shuwa Xu for general discussions. We thank Susan Abmayr for sns lines. Imaging was performed in the Biological Imaging Facility, with the support of the Caltech Beckman Institute and the Arnold and Mabel Beckman Foundation. Protein expression in baculovirus and Expi293 cells was performed at the Caltech Protein Expression Center (Jost Vielmetter, director). This work was supported by grants from the NIH to KZ, R37 NS028182 and RO1 NS096509 and by a Gordon Ross postdoctoral fellowship to NB. The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication. 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. Author contributions: Namrata Bali, H.K.L. performed the embryo GOF screen. N.B. performed all other experiments., Investigation, Writing - original draft, Writing - review and editing; Hyung-Kook (Peter) Lee, Investigation; Kai Zinn, Conceptualization, Funding acquisition, Methodology, Supervision, Writing - original draft, Writing - review and editing.

Attached Files

Published - elife-71469-v2.pdf

Submitted - 2020.11.03.367540v1.full.pdf

Supplemental Material - elife-71469-supp-v1.zip

Supplemental Material - elife-71469-transrepform1-v2.docx


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August 20, 2023
December 22, 2023