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

Bali, Namrata and Lee, Hyung-Kook (Peter) and Zinn, Kai (2020) Sticks and Stones, a conserved cell surface ligand for the Type IIa RPTP Lar, regulates neural circuit wiring in Drosophila. . (Unpublished) https://resolver.caltech.edu/CaltechAUTHORS:20201106-105648139

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Abstract

Control of tyrosine phosphorylation is an essential element of many cellular processes, including proliferation, differentiation neurite outgrowth, and synaptogenesis. Receptor-like protein-tyrosine phosphatases (RPTPs) have cytoplasmic phosphatase domains and cell adhesion molecule (CAM)-like extracellular domains that interact with cell-surface ligands and/or co-receptors. We identified a new ligand for the Drosophila Lar RPTP, the immunoglobulin superfamily CAM Sticks and Stones (Sns). Lar is orthologous to the three Type IIa mammalian RPTPs, PTPRF (LAR), PTPRD (PTPδ), and PTPRS (PTPσ). Lar and Sns bind to each other in embryos and in vitro. The human Sns ortholog, Nephrin, binds to PTPRD and PTPRF. Genetic interaction studies show that Sns is essential to Lar′s functions in several developmental contexts in the larval and adult nervous systems. In the larval neuromuscular system, Lar and sns transheterozygotes (Lar/sns transhets) have synaptic defects like those seen in Lar mutants and Sns knockdown animals. Lar and Sns reporters are both expressed in motor neurons and not in muscles, so Lar and Sns likely act in cis (in the same neurons). Lar mutants and Lar/sns transhets have identical axon guidance defects in the larval mushroom body in which Kenyon cell axons fail to stop at the midline and do not branch. Pupal Kenyon cell axon guidance is similarly affected, resulting in adult mushroom body defects. Lar is expressed in larval and pupal Kenyon cells, but Sns is not, so Lar-Sns interactions in this system must be in trans (between neurons). Lastly, R7 photoreceptor axons in Lar mutants and Lar/sns transhets fail to innervate the correct M6 layer of the medulla in the optic lobe. Lar acts cell-autonomously in R7s, while Sns is only in lamina and medulla neurons that arborize near the R7 target layer. Therefore, the Lar-Sns interactions that control R7 targeting also occur in trans.


Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription
https://doi.org/10.1101/2020.11.03.367540DOIDiscussion Paper
ORCID:
AuthorORCID
Zinn, Kai0000-0002-6706-5605
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This version posted November 5, 2020. We thank Michael Anaya for discussions about in vitro binding assays, and Kaushiki Menon and Shuwa Xu for general discussions. We thank Susan Abmayr for sns lines. This work was supported by a grant from the NIH to K.Z., R37 NS28182.
Funders:
Funding AgencyGrant Number
NIHR37 NS28182
Record Number:CaltechAUTHORS:20201106-105648139
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20201106-105648139
Official Citation:Sticks and Stones, a conserved cell surface ligand for the Type IIa RPTP Lar, regulates neural circuit wiring in Drosophila. Namrata Bali, Hyung-Kook (Peter) Lee, Kai Zinn. bioRxiv 2020.11.03.367540; doi: https://doi.org/10.1101/2020.11.03.367540
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:106477
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:06 Nov 2020 19:27
Last Modified:06 Nov 2020 19:27

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