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The Journal of Neuroscience, January 4, 2006, 26(1):152-157; doi:10.1523/JNEUROSCI.4164-05.2006

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Local Synthesis of Actin-Binding Protein -Thymosin Regulates Neurite Outgrowth

Ronald E. van Kesteren,^1 * Christopher Carter,^2 * Helga M. G. Dissel,¹ Jan van Minnen,¹ Yvonne Gouwenberg,¹ Naweed I. Syed,³ Gaynor E. Spencer,² and August B. Smit¹

¹Department of Molecular and Cellular Neurobiology, Research Institute Neurosciences, Vrije Universiteit, 1081 HV Amsterdam, The Netherlands, ²Department of Biological Sciences, Brock University, St. Catharines, Ontario, Canada L2S 3A1, and ³Respiratory and Neuroscience Research Groups, Faculty of Medicine, University of Calgary, Alberta, Canada T2N 4N1

Local protein synthesis plays an essential role in the regulation of various aspects of axonal and dendritic function in adult neurons. At present, however, there is no direct evidence that local protein translation is functionally contributing to neuronal outgrowth. Here, we identified the mRNA encoding the actin-binding protein -thymosin as one of the most abundant transcripts in neurites of outgrowing neurons in culture. -Thymosin mRNA is not evenly distributed in neurites, but appears to accumulate at distinct sites such as turning points and growth cones. Using double-stranded RNA knockdown, we show that reducing -thymosin mRNA levels results in a significant increase in neurite outgrowth, both in neurites of intact cells and in isolated neurites. Together, our data demonstrate that local synthesis of -thymosin is functionally involved in regulating neuronal outgrowth.

Key words: neurite outgrowth; local translation; local protein synthesis; actin cytoskeleton; actin-binding protein; -thymosin

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Received May 17, 2005; revised November 7, 2005; accepted November 7, 2005.

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