OMgp LRR281～228：OMgp神经突起生长抑制功能的主要结构域

OMgp(oligodendrocyte-myelin glycoprotein)可以通过与MAG、nogo-66等神经再生抑制因子竞争结合同一受体NgR而诱使生长锥溃变和抑制神经突起的生长。以前的研究表明，在OMgp与NgR结合抑制神经突起生长的过程中，OMgp的亮氨酸富含重复序列(LRR)是必需的。为进一步了解OMgp LRR在神经突起生长中的作用及其结构与功能之间的关系，采用PCR-定点突变法对OMgp LRR结构域分段删除，表达了删除不同基因片段后的OMgp LRR蛋白，通过对表达有NgR的CHO细胞(NgR-CHO)的黏附实验和对原代培养神经细胞的抑制实验对其功能进行了研究。结果显示，分别删除了OMgp 25～56、57～133、134～180位氨基酸的OMgp LRR蛋白仍具有结合NgR-CHO和抑制原代培养的神经元突起生长的作用；而删除了第181～228位氨基酸的OMgp LRR蛋白则失去了对原代培养神经元的生长抑制作用，但仍然具有结合NgR的能力。表明OMgp181～228在OMgp的功能中具有重要的意义。删除了第181～228位氨基酸的OMgp LRR蛋白可望作为OMgp的竞争性抑制剂，用于中枢神经系统损伤后神经再生的治疗。

OMgp LRR181-228: The Predominant Domain of OMgp in Neurite Outgrowth Inhibition

Several observations suggest that the leucine-rich repeats (LRR) domain of oligodendrocyte-myelin glycoprotein (OMgp) may play an important role in inhibition of neurite outgrowth and axonal regeneration after brain injury. To better understand structure-function relationships for the OMgp LRR domain and its effects in neurite regeneration, distinct OMgp leucine-rich repeat were deleted by PCR based site-directed mutagenesis. The gene deleted OMgp LRR fragments were expressed with GST protein and the expressed proteins were used to culture with NgR-expressing CHO and hippocampal neurons. Results show that the deletion of OMgp amino acid residues 25-56, 57-133,134-180 did not interrupt its effects in binding NgR-expressing CHO and inhibiting hippocampal neurons growth. But the fragment deleted amino acid residues 181-228 can only bind with NgR-expressing CHO and lost the effect of neurite outgrowth inhibition. Results suggest that the OMgp amino acid 181-228 is the predominant domain in neurite outgrowth inhibition of OMgp. The OMgp LRR fragment without amino acid residues 181-228 may be a potent reagent for encouraging regeneration in the adult central nervous system following injury.