1. The RNA-binding protein Musashi controls axon compartment-specific synaptic connectivity through ptp69D mRNA poly(A)-tailing.
- Author
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Landínez-Macías M, Qi W, Bratus-Neuenschwander A, Müller M, and Urwyler O
- Subjects
- 3' Untranslated Regions, Animals, Drosophila growth & development, Drosophila metabolism, Drosophila Proteins antagonists & inhibitors, Drosophila Proteins genetics, Larva metabolism, Morphogenesis, Neurons metabolism, Protein Binding, RNA Interference, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Small Interfering metabolism, RNA-Binding Proteins antagonists & inhibitors, RNA-Binding Proteins genetics, Receptor-Like Protein Tyrosine Phosphatases antagonists & inhibitors, Receptor-Like Protein Tyrosine Phosphatases genetics, Receptors, Odorant metabolism, Axons physiology, Drosophila Proteins metabolism, Poly A metabolism, RNA-Binding Proteins metabolism, Receptor-Like Protein Tyrosine Phosphatases metabolism, Synapses physiology
- Abstract
Synaptic targeting with subcellular specificity is essential for neural circuit assembly. Developing neurons use mechanisms to curb promiscuous synaptic connections and to direct synapse formation to defined subcellular compartments. How this selectivity is achieved molecularly remains enigmatic. Here, we discover a link between mRNA poly(A)-tailing and axon collateral branch-specific synaptic connectivity within the CNS. We reveal that the RNA-binding protein Musashi binds to the mRNA encoding the receptor protein tyrosine phosphatase Ptp69D, thereby increasing poly(A) tail length and Ptp69D protein levels. This regulation specifically promotes synaptic connectivity in one axon collateral characterized by a high degree of arborization and strong synaptogenic potential. In a different compartment of the same axon, Musashi prevents ectopic synaptogenesis, revealing antagonistic, compartment-specific functions. Moreover, Musashi-dependent Ptp69D regulation controls synaptic connectivity in the olfactory circuit. Thus, Musashi differentially shapes synaptic connectivity at the level of individual subcellular compartments and within different developmental and neuron type-specific contexts., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2021
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