A Requirement for Mena, an Actin Regulator, in Local mRNA Translation in Developing Neurons
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nihms890865.pdf
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Author(s)
Tatarakis, Antonios
Vidaki, Marina
Drees, Frauke
Saxena, Tanvi
Lanslots, Erwin
Taliaferro, Matthew J.
Burge, Christopher B
Wang, Eric T
Gertler, Frank
Date Issued
July 2017
Journal
Neuron
Publisher
Elsevier BV
Citation
Vidaki, Marina et al. “A Requirement for Mena, an Actin Regulator, in Local mRNA Translation in Developing Neurons.” Neuron 95, 3 (August 2017): 608–622 © 2017 Elsevier Inc
Version
Author's final manuscript
Abstract
During neuronal development, local mRNA translation is required for axon guidance and synaptogenesis, and dysregulation of this process contributes to multiple neurodevelopmental and cognitive disorders. However, regulation of local protein synthesis in developing axons remains poorly understood. Here, we uncover a novel role for the actin-regulatory protein Mena in the formation of a ribonucleoprotein complex that involves the RNA-binding proteins HnrnpK and PCBP1 and regulates local translation of specific mRNAs in developing axons. We find that translation of dyrk1a, a Down syndrome- and autism spectrum disorders-related gene, is dependent on Mena, both in steady-state conditions and upon BDNF stimulation. We identify hundreds of additional mRNAs that associate with the Mena complex, suggesting that it plays broader role(s) in post-transcriptional gene regulation. Our work establishes a dual role for Mena in neurons, providing a potential link between regulation of actin dynamics and local translation. Keywords: Mena; ENAH; Ena/VASP; developing axon; growth cone; axon guidance; local translation; ribonucleoprotein; Dyrk1a
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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Creative Commons Attribution-NonCommercial-NoDerivs License
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DOI of Published Version
https://doi.org/10.1016/J.NEURON.2017.06.048
