These authors contributed equally to this work.
Rufy3, a protein specifically expressed in neurons, interacts with actin-bundling protein Fascin to control the growth of axons
Version of Record online: 19 MAY 2014
© 2014 International Society for Neurochemistry
Journal of Neurochemistry
Volume 130, Issue 5, pages 678–692, September 2014
How to Cite
J. Neurochem. (2014) 130, 678–692.
Cover Image for this issue: doi: 10.1111/jnc.12580.
- Issue online: 20 AUG 2014
- Version of Record online: 19 MAY 2014
- Accepted manuscript online: 10 APR 2014 11:17AM EST
- Manuscript Accepted: 7 APR 2014
- Manuscript Revised: 2 APR 2014
- Manuscript Received: 22 NOV 2013
- Chinese Academy of Sciences. Grant Number: XDA01010102
- National Natural Science Foundation. Grant Number: 91019023
- National High Technology Research and Development Program of China. Grant Numbers: 2010CB945200, 2011DFB300100, 2011CB965101, 2009CB941103
- axon length;
- growth cones;
For our nervous system to function properly, each neuron must generate a single axon and elongate the axon to reach its target. It is known that actin filaments and their dynamic interaction with microtubules within growth cones play important roles in inducing axon extension. However, it remains unclear how cytoskeletal dynamics is controlled in growth cones. In this study, we report that Rufy3, a RUN domain-containing protein, is a neuron-specific and actin filament-relevant protein. We find that the appropriate expression of Rufy3 in mouse hippocampal neurons is required for the development of a single axon and axon growth. Our results show that Rufy3 specifically interacts with actin filament-binding proteins, such as Fascin, and colocalizes with Fascin in growth cones. Knockdown of Rufy3 impairs the distribution of Fascin and actin filaments, accompanied by an increased proportion of neurons with multiple axons and a decrease in the axon length. Therefore, Rufy3 may be particularly important for neuronal axon elongation by interacting with Fascin to control actin filament organization in axonal growth cones.
We propose that Rufy3 may control mouse neuron axon development through its specific interaction with Fascin and Drebrin. Over-expression of Rufy3 (Rufy3 OE) leads to longer axons and expands the distribution of Drebrin to almost the entire growth cone. In contrast, knockdown of Rufy3 (Rufy3 RNAi) results in shortened axons and enhanced the percentage of mutipolar neurons. Moreover, silencing of Rufy3 reduces and restricts the expression of Fascin and F-actin to the edge of the growth cone. These findings provide new insights into the molecular regulation of axonal outgrowth and cell polarization in neurons.