Volume 22, No 6, Jun 2012
ISSN: 1001-0602
EISSN: 1748-7838 2018
impact factor 17.848*
(Clarivate Analytics, 2019)
Volume 22 Issue 6, June 2012: 954-972
ORIGINAL ARTICLES
Laminin/β1 integrin signal triggers axon formation by promoting microtubule assembly and stabilization
Wen-Liang Lei1, Shi-Ge Xing2, Cai-Yun Deng1, Xiang-Chun Ju1, Xing-Yu Jiang2 and Zhen-Ge Luo1
1Institute of Neuroscience and Key State Laboratory of Neuroscience, Chinese Academy of Sciences, Shanghai 200031, China
2National Center for NanoScience and Technology of China, Beijing 100190, China
Correspondence: Zhen-Ge Luo,(zgluo@ion.ac.cn)
Axon specification during neuronal polarization is closely associated with increased microtubule stabilization in one of the neurites of unpolarized neuron, but how this increased microtubule stability is achieved is unclear. Here, we show that extracellular matrix (ECM) component laminin promotes neuronal polarization via regulating directional microtubule assembly through β1 integrin (Itgb1). Contact with laminin coated on culture substrate or polystyrene beads was sufficient for axon specification of undifferentiated neurites in cultured hippocampal neurons and cortical slices. Active Itgb1 was found to be concentrated in laminin-contacting neurites. Axon formation was promoted and abolished by enhancing and attenuating Itgb1 signaling, respectively. Interestingly, laminin contact promoted plus-end microtubule assembly in a manner that required Itgb1. Moreover, stabilizing microtubules partially prevented polarization defects caused by Itgb1 downregulation. Finally, genetic ablation of Itgb1 in dorsal telencephalic progenitors caused deficits in axon development of cortical pyramidal neurons. Thus, laminin/Itgb1 signaling plays an instructive role in axon initiation and growth, both
in vitro and
in vivo, through the regulation of microtubule assembly. This study has established a linkage between an extrinsic factor and intrinsic cytoskeletal dynamics during neuronal polarization.
Cell Research (2012) 22:954-972. doi:10.1038/cr.2012.40; published online 20 March 2012
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