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

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. He...

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Main Authors: Tatarakis, Antonios (Author), Vidaki, Marina (Contributor), Drees, Frauke (Contributor), Saxena, Tanvi (Contributor), Lanslots, Erwin (Contributor), Taliaferro, Matthew J. (Contributor), Burge, Christopher B (Contributor), Wang, Eric T (Contributor), Gertler, Frank (Contributor)
Other Authors: Massachusetts Institute of Technology. Department of Biology (Contributor), Koch Institute for Integrative Cancer Research at MIT (Contributor)
Format: Article
Language:English
Published: Elsevier BV, 2018-08-22T19:53:02Z.
Subjects:
Online Access:Get fulltext
LEADER 02543 am a22003733u 4500
001 117494
042 |a dc 
100 1 0 |a Tatarakis, Antonios  |e author 
100 1 0 |a Massachusetts Institute of Technology. Department of Biology  |e contributor 
100 1 0 |a Koch Institute for Integrative Cancer Research at MIT  |e contributor 
100 1 0 |a Vidaki, Marina  |e contributor 
100 1 0 |a Drees, Frauke  |e contributor 
100 1 0 |a Saxena, Tanvi  |e contributor 
100 1 0 |a Lanslots, Erwin  |e contributor 
100 1 0 |a Taliaferro, Matthew J.  |e contributor 
100 1 0 |a Burge, Christopher B  |e contributor 
100 1 0 |a Wang, Eric T  |e contributor 
100 1 0 |a Gertler, Frank  |e contributor 
700 1 0 |a Vidaki, Marina  |e author 
700 1 0 |a Drees, Frauke  |e author 
700 1 0 |a Saxena, Tanvi  |e author 
700 1 0 |a Lanslots, Erwin  |e author 
700 1 0 |a Taliaferro, Matthew J.  |e author 
700 1 0 |a Burge, Christopher B  |e author 
700 1 0 |a Wang, Eric T  |e author 
700 1 0 |a Gertler, Frank  |e author 
245 0 0 |a A Requirement for Mena, an Actin Regulator, in Local mRNA Translation in Developing Neurons 
260 |b Elsevier BV,   |c 2018-08-22T19:53:02Z. 
856 |z Get fulltext  |u http://hdl.handle.net/1721.1/117494 
520 |a 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 
520 |a National Institutes of Health (U.S.) (Grant U01-CA184897) 
520 |a National Cancer Institute (U.S.) (Grant P30-CA14051) 
655 7 |a Article 
773 |t Neuron