Sticks and Stones, a conserved cell surface ligand for the Type IIa RPTP Lar, regulates neural circuit wiring inDrosophila
| Autor: | Namrata Bali, Kai Zinn, Hyung-Kook Peter Lee |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Motor Neurons
animal structures Kenyon cell General Immunology and Microbiology Neurite General Neuroscience Neurogenesis Synaptogenesis Receptor-Like Protein Tyrosine Phosphatases General Medicine PTPRF Biology Ligands General Biochemistry Genetics and Molecular Biology Cell biology Mushroom bodies Animals Drosophila Proteins Immunoglobulin superfamily Drosophila Axon guidance PTPRS |
| Popis: | 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 theDrosophilaLar 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 andin 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,Larandsnstransheterozygotes (Lar/snstranshets) have synaptic defects like those seen inLarmutants and Sns knockdown animals. Lar and Sns reporters are both expressed in motor neurons and not in muscles, so Lar and Sns likely act incis(in the same neurons).Larmutants andLar/snstranshets 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 intrans(between neurons). Lastly, R7 photoreceptor axons inLarmutants andLar/snstranshets 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 intrans. |
| Databáze: | OpenAIRE |
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