Transforming growth factor-beta 2 is anterogradely and retrogradely transported in motoneurons and up-regulated after nerve injury

Transforming growth factor-beta 2 is anterogradely and retrogradely transported in motoneurons and up-regulated after nerve injury
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DOI:
10.1016/s0306-4522(00)00084-1
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发表时间:
2000-01-01
期刊:
影响因子:
3.3
通讯作者:
Hendry, IA
Hendry, IA
中科院分区:
医学3区
文献类型:
--
作者:
Jiang, Y;McLennan, IS;Hendry, IA

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运动神经元的生存依赖于它们从肌纤维和各种其他细胞类型中获得持续的营养支持。已经确定了许多假定的生存因素,并建立了一套标准,根据这些标准可以评估这些候选人。这些标准包括因子及其受体在适当位置的需要,以及因子或其第二信息逆行运输的需要。在本文中,我们证明了一种多功能细胞因子,转化生长因子- β 2,似乎符合这些标准。通过逆转录聚合酶链反应和免疫组织化学确定了转化生长因子- β 2及其受体在神经肌肉系统中的位置,运动神经元合成了三种参与转化生长因子- β 2信号传导的蛋白质(I型和IT型转化生长因子- β受体和β多糖),并顺行运输,在那里它们被插入轴突膜和神经末梢。在肌肉纤维、运动神经元和损伤神经的突触部分检测到转化生长因子- β 2,表明运动神经元可能暴露于多种潜在冗余的转化生长因子- β 2来源。双结扎实验证明运动神经元在轴突上下传递转化生长因子- β 2。转化生长因子- β 2及其受体的顺行运输,加上大多数运动神经元的线粒体位于轴突的事实,提出了凋亡起始的抑制是局限于细胞体还是发生在整个神经元长度上的问题。(c) 2000 ibro。Elsevier Science Ltd.出版。
The survival of motoneurons is dependent on them receiving continual trophic support from muscle fibres and various other cell types. Numerous putative survival factors have been identified and a set of criteria established by which these candidates can be assessed. These criteria include the need for the factor and its receptors to be in appropriate locations and for the factor or its second message to be retrogradely transported. In this paper, we demonstrate that a multifunctional cytokine, transforming growth factor-beta 2, appears to meet these criteria. The locations of the transforming growth factor-beta 2 and its receptors in the neuromuscular system were determined by reverse transcriptase-polymerase chain reaction and immunohistochemistry Motoneurons were shown to synthesize the three proteins involved in transforming growth factor-beta 2 signalling (types I and IT transforming growth factor-beta receptor and betaglycan) and to transport them anterogradely, where they were inserted into the axonal membrane and nerve terminal. Transforming growth factor-beta 2 was detected in the synaptic portions of muscle fibres, motoneurons and in injured nerves, indicating that motoneurons may be exposed to multiple and potentially redundant sources of transforming growth factor-beta 2. Double-ligation experiments were used to demonstrate that motoneurons transport transforming growth factor-beta 2 up and down their axons.The anterograde transport of both transforming growth factor-beta 2 and its receptors, coupled with the fact that most of a motoneuron's mitochondria are located in the axon, raises the issue of whether the repression of the initiation of apoptosis is restricted to the cell body or occurs along the entire length of a neuron. (C) 2000 IBRO. Published by Elsevier Science Ltd.