Elongation of Axons during regeneration involves retinal crystallin β b2 (crybb2)
Elongation of Axons during regeneration involves retinal crystallin β b2 (crybb2)
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DOI：
10.1074/mcp.m600245-mcp200
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发表时间：
2007-05-01
影响因子：
7
通讯作者：
Thanos, Solon
中科院分区：
文献类型：
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作者：
Liedtke, Thomas;Schwamborn, Jens Christian;Thanos, Solon
成年视网膜神经节细胞（RGCs）在体外可以再生轴突。利用蛋白质组学，我们发现培养视网膜的上清液中含有晶体蛋白的同种型，其中晶体蛋白β b2（crybb 2）在再生视网膜中明显上调。免疫组织化学显示crybb在视网膜内的表达，包括在丝状伪足突起和RGCs的轴突中。crybb 2在RGCs和海马神经元中的克隆和过表达增加了轴突生成，这反过来又可以被β-晶体蛋白抗体阻断。来自crybb 2转染细胞培养物的条件培养基也支持轴突的生长。最后，绿色荧光蛋白标记的crybb 2融合蛋白的摄取的真实的时间成像显示该蛋白质变得内化。这些数据首次表明轴突再生与crybb 2运动有关。结果表明，神经元晶体蛋白构成一类新的神经突促进因子，可能通过自分泌机制运作，它们可用于神经退行性疾病。
Adult retinal ganglion cells (RGCs) can regenerate their axons in vitro. Using proteomics, we discovered that the supernatants of cultured retinas contain isoforms of crystallins with crystallin beta b2 (crybb2) being clearly up-regulated in the regenerating retina. Immunohistochemistry revealed the expression of crybb within the retina, including in filopodial protrusions and axons of RGCs. Cloning and overexpression of crybb2 in RGCs and hippocampal neurons increased axonogenesis, which in turn could be blocked with antibodies against beta-crystallin. Conditioned medium from crybb2-transfected cell cultures also supported the growth of axons. Finally real time imaging of the uptake of green fluorescent protein-tagged crybb2 fusion protein showed that this protein becomes internalized. These data are the first to show that axonal regeneration is related to crybb2 movement. The results suggest that neuronal crystallins constitute a novel class of neurite-promoting factors that likely operate through an autocrine mechanism and that they could be used in neurodegenerative diseases.