The Nab2 RNA-binding protein patterns dendritic and axonal projections through a planar cell polarity-sensitive mechanism

• Type of Material: Article
• Authors: Edwin B Corgiat, Emory University; Sara M List, Emory University; Christopher J Rounds, Emory University; Dehong Yu, Emory University; Ping Chen, Emory University; Anita Corbett, Emory University; Kenneth Moberg, Emory University
• Language: English
• Date: 2022-05-12
• Publisher: OXFORD UNIV PRESS INC
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1093/g3journal/jkac100
• Title of Journal or Parent Work: G3-GENES GENOMES GENETICS
• Volume: 12
• Issue: 6
• Grant/Funding Information: Financial support from the National Institutes of Health as follows: 5F31NS110312, 5F31HD088043, and 5R01MH107305.; Research reported in this publication was supported in part by the Emory University Integrated Cellular Imaging Microscopy Core of the Emory Neuroscience NINDS Core Facilities grant, 5P30NS055077.
• Keywords: dendrite; ddaC neuron; RNA-binding protein; MUSHROOM BODY; Genetics & Heredity; Nab2; planar cell polarity; axon; GENE; NETWORK; DROSOPHILA; mushroom body; ENRICHR; PATHWAY; TRANSLATION; intellectual disability; Science & Technology; BRANCH EXTENSION; VANGL2; LOCALIZATION; Life Sciences & Biomedicine

Abstract

RNA-binding proteins support neurodevelopment by modulating numerous steps in post-transcriptional regulation, including splicing, export, translation, and turnover of mRNAs that can traffic into axons and dendrites. One such RNA-binding protein is ZC3H14, which is lost in an inherited intellectual disability. The Drosophila melanogaster ZC3H14 ortholog, Nab2, localizes to neuronal nuclei and cytoplasmic ribonucleoprotein granules and is required for olfactory memory and proper axon projection into brain mushroom bodies. Nab2 can act as a translational repressor in conjunction with the Fragile-X mental retardation protein homolog Fmr1 and shares target RNAs with the Fmr1- interacting RNA-binding protein Ataxin-2. However, neuronal signaling pathways regulated by Nab2 and their potential roles outside of mushroom body axons remain undefined. Here, we present an analysis of a brain proteomic dataset that indicates that multiple planar cell polarity proteins are affected by Nab2 loss, and couple this with genetic data that demonstrate that Nab2 has a previously unappreciated role in restricting the growth and branching of dendrites that elaborate from larval body-wall sensory neurons. Further analysis confirms that Nab2 loss sensitizes sensory dendrites to the genetic dose of planar cell polarity components and that Nab2-planar cell polarity genetic interactions are also observed during Nab2-dependent control of axon projection in the central nervous system mushroom bodies. Collectively, these data identify the conserved Nab2 RNA-binding protein as a likely component of post-transcriptional mechanisms that limit dendrite growth and branching in Drosophila sensory neurons and genetically link this role to the planar cell polarity pathway. Given that mammalian ZC3H14 localizes to dendritic spines and controls spine density in hippocampal neurons, these Nab2-planar cell polarity genetic data may highlight a conserved path through which Nab2/ZC3H14 loss affects morphogenesis of both axons and dendrites in diverse species.