Axotomy induces axonogenesis in hippocampal neurons through STAT3

作者：Ohara R; Fujita Y; Hata K; Nakagawa M; Yamashita T^*

来源：Cell Death & Disease, 2011, 2: e175.

DOI：10.1038/cddis.2011.59

• axonal injury
• axonogenesis
• STAT3
• dynein
• importin

After axotomy of embryonic hippocampal neurons in vitro, some of the axotomized axons lose their identity, and new axons arise and grow. This axotomy-induced axonogenesis requires importin, suggesting that some injury-induced signals are transported via axons to elicit axonogenesis after axotomy. In this study, we show that STAT3 is activated in response to axotomy. Because STAT3 was co-immunoprecipitated with importin beta in the axotomized neurons, we suggest that STAT3 is retrogradely transported as molecular cargo of importin alpha/beta heterodimers. Indeed, inhibition of importin alpha binding with STAT3 resulted in the attenuation of axonogenesis. Silencing STAT3 blocked the axonogenesis, demonstrating that STAT3 is necessary for axotomy-induced axonogenesis. Furthermore, the overexpression of STAT3 enhanced axotomy-induced axonogenesis. Taken together, these results demonstrate that activation and retrograde transport of STAT3 in injured axons have key roles in the axotomy-induced axonogenesis of hippocampal neurons. Cell Death and Disease (2011) 2, e175; doi:10.1038/cddis.2011.59; published online 23 June 2011

• 出版日期2011-6