An involvement of damage induced neuronal endopeptidase DINE in construction of neuro-muscular junction.

我们利用周围神经损伤模型鉴定了神经损伤诱导的神经元内肽酶（DINE）。DINE在中枢神经系统和旁神经系统神经元细胞中都是对神经损伤的反应。为了揭示这种肽酶的功能，我们制作了DINE敲除小鼠。由于呼吸问题，这些小鼠在出生后立即死亡。我们发现，缺乏DINE的小鼠表现出神经末梢分支的神经支配不良，只有少数神经肌肉连接（NMJ），这表明DINE是远端轴突进入肌肉以建立NMJ的关键分子。为了揭示表型背后的机制，我们将dine缺陷神经元和雪旺细胞共培养，发现dine缺陷影响轴突-雪旺相互作用和雪旺成熟。这些数据表明，DINE与雪旺细胞的成熟以及NMJ的适当构建有关。

We have identified nerve injury induced neuronal endopeptidase (DINE) using peripheral nerve injury model. DINE is induced in bothCNS and PNS neuronal cells in response to nerve injury. To reveal a function of this peptidase, we have made DINE knockout mice. These mice were lethal immediately after birth due to respiration problem. We identified that DINE-deficient mice exhibited the poor innervation of final branching of nerve and only a few neuromuscular junctions (NMJ), suggesting that DINE is a crucial molecule in distal axon arborization into muscle to establish NMJ. To reveal mechanisms underlying the phenotypes, we co-cultured DINE-deficient neurons and Schwann cells, and found that DINE-deficiency affected on axon-Schwann interaction and Schwann maturation. These data suggests that DINE is implicated in maturation of Schwann cells as well as proper construction of NMJ.