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Neuron. 2017 Aug 2;95(3):608-622.e5. doi: 10.1016/j.neuron.2017.06.048. Epub 2017 Jul 20.

A Requirement for Mena, an Actin Regulator, in Local mRNA Translation in Developing Neurons.

Author information

1
The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: mvidaki@mit.edu.
2
The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
3
The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
4
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
5
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
6
The Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA. Electronic address: fgertler@mit.edu.

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:

Dyrk1a; ENAH; Ena/VASP; Mena; axon guidance; developing axon; growth cone; local translation; ribonucleoprotein

PMID:
28735747
PMCID:
PMC5616167
DOI:
10.1016/j.neuron.2017.06.048
[Indexed for MEDLINE]
Free PMC Article

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