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Published online June 2, 2008
doi:10.1083/jcb.200712138
The Journal of Cell Biology, Vol. 181, No. 5, 817-829
The Rockefeller University Press, 0021-9525 $30.00
© 2008 Shimada et al.
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Article

 Shootin1 interacts with actin retrograde flow and L1-CAM to promote axon outgrowth

Tadayuki Shimada1, Michinori Toriyama1, Kaori Uemura1, Hiroyuki Kamiguchi3, Tadao Sugiura2, Naoki Watanabe4, and Naoyuki Inagaki1

1 Division of Signal Transduction and 2 Biomedical Imaging and Informatics, Nara Institute of Science and Technology, Ikoma 630-0192, Japan
3 Laboratory for Neuronal Growth Mechanisms, Brain Science Institute, Institute of Physical and Chemical Research (RIKEN), Saitama 351-0198, Japan
4 Department of Pharmacology, Kyoto University Faculty of Medicine, Kyoto 606-8501, Japan

Correspondence to N. Inagaki: ninagaki{at}bs.naist.jp

Actin polymerizes near the leading edge of nerve growth cones, and actin filaments show retrograde movement in filopodia and lamellipodia. Linkage between actin filament retrograde flow and cell adhesion molecules (CAMs) in growth cones is thought to be one of the mechanisms for axon outgrowth and guidance. However, the molecular basis for this linkage remains elusive. Here, we show that shootin1 interacts with both actin filament retrograde flow and L1-CAM in axonal growth cones of cultured rat hippocampal neurons, thereby mediating the linkage between them. Impairing this linkage, either by shootin1 RNA interference or disturbing the interaction between shootin1 and actin filament flow, inhibited L1-dependent axon outgrowth, whereas enhancing the linkage by shootin1 overexpression promoted neurite outgrowth. These results strengthen the actin flow–CAM linkage model ("clutch" model) for axon outgrowth and suggest that shootin1 is a key molecule involved in this mechanism.

Abbreviations used in this paper: CAM, cell adhesion molecule; DIC, differential interference contrast; NES, nuclear export signal; PI 3-kinase, phosphoinositide-3-kinase; shRNA, short hairpin RNA.

© 2008 Shimada et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jcb.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).


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