Lyons W E, Steiner J P, Snyder S H, Dawson T M
Division of Toxicological Sciences, Johns Hopkins School of Hygiene and Public Health, Baltimore, Maryland, USA.
J Neurosci. 1995 Apr;15(4):2985-94. doi: 10.1523/JNEUROSCI.15-04-02985.1995.
Immunophilins are a group of proteins that serve as receptors for the immunosuppressant drugs cyclosporin A and FK506. The immunophilin designated FK-506 binding protein-12 (FKBP-12) is concentrated more than 10 times higher in the brain than in immune tissues. The complex of FK506 and FKBP-12 inhibits the calcium activated phosphatase, calcineurin, increasing phosphorylated levels of calcineurin substrates with growth associated protein-43 (GAP-43), being most prominent in the brain. We now demonstrate an association of FKBP-12 with neuronal regeneration and GAP-43 disposition. Facial nerve crush markedly augments expression of FKBP-12 mRNA in the facial nucleus with a time course paralleling changes in GAP-43 mRNA. Following sciatic nerve lesions, similar increases in FKBP-12 mRNA occur in lumbar motor neurons and dorsal root ganglia neuronal cells. Increased FKBP-12 expression appears linked to regeneration rather than degeneration as facial nerve lesions elicited by ricin injection, which produce neuronal death without regeneration, fail to augment FKBP-12 expression in the facial nucleus. The time course for accumulation of FKBP-12 in sciatic nerve segments following nerve crush indicates rapid axonal transport at a rate similar to GAP-43.
亲免素是一类蛋白质，可作为免疫抑制剂环孢菌素A和FK506的受体。名为FK - 506结合蛋白 - 12（FKBP - 12）的亲免素在脑中的浓度比在免疫组织中高10倍以上。FK506与FKBP - 12的复合物可抑制钙激活磷酸酶钙调神经磷酸酶，增加钙调神经磷酸酶底物与生长相关蛋白 - 43（GAP - 43）的磷酸化水平，这在脑中最为显著。我们现在证明FKBP - 12与神经元再生及GAP - 43分布有关。面神经挤压明显增强了面神经核中FKBP - 12 mRNA的表达，其时间进程与GAP - 43 mRNA的变化平行。坐骨神经损伤后，腰运动神经元和背根神经节神经元细胞中FKBP - 12 mRNA也有类似增加。FKBP - 12表达增加似乎与再生而非变性有关，因为蓖麻毒素注射引起的面神经损伤导致神经元死亡而无再生，未能增强面神经核中FKBP - 12的表达。神经挤压后FKBP - 12在坐骨神经节段中的积累时间进程表明其以与GAP - 43相似的速率进行快速轴突运输。
