Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75NTR-mediated axon guidance.

Pro-neurotrophins secreted from retinal ganglion cell axons are necessary for ephrinA-p75NTR-mediated axon guidance.
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DOI:
10.1186/1749-8104-5-30
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发表时间:
2010-11-02
期刊:
影响因子:
3.6
通讯作者:
Drescher U
Drescher U
中科院分区:
生物学3区
文献类型:
--
作者:
Marler KJ;Poopalasundaram S;Broom ER;Wentzel C;Drescher U

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视网膜顶图的形成是通过特定的地形引导和视网膜轴突在目标区域的分支而形成的。这一过程部分由视网膜轴突上表达的ephrinAs的反向信号传导控制。作为糖基磷脂酰肌醇锚定分子,ephrinAs需要跨膜共受体来发挥这一功能,最近提出了两种神经营养因子受体p75NTR和TrkB。我们在这里表明,这些受体的配体,脑源性神经营养因子前体(proBDNF)及其加工形式BDNF,分别通过诱导相应的神经营养因子受体- ephrina复合物来拮抗控制视网膜轴突分支。此外,通过添加针对proBNDF的前结构域或p75NTR的可溶性细胞外结构域的抗体来清除嗜前eurotrophins,在条纹实验中消除了排斥性ephrinA的反向信号。这表明视网膜细胞分泌嗜前eurotrophins,诱导ephrinA-p75NTR相互作用,并使排斥轴突引导。proBDNF和BDNF的拮抗功能提出了地形分支是通过局部控制嗜前粒细胞加工来控制的可能性。
Retinotectal map formation develops via topographically specific guidance and branching of retinal axons in their target area. This process is controlled, in part, by reverse signalling of ephrinAs expressed on retinal axons. As glycosylphosphatidylinositol-anchored molecules, ephrinAs require transmembrane co-receptors to exert this function, for which the two neurotrophin receptors, p75NTR and TrkB, were recently proposed. We show here that the ligands for these receptors, the brain-derived neurotrophic factor precursor (proBDNF) and its processed form, BDNF, respectively, control the branching of retinal axons antagonistically, which they mediate by inducing the corresponding neurotrophin receptor-ephrinA complexes. Moreover, scavenging proneurotrophins, by adding antibodies specific for the pro-domain of proBNDF or a soluble extracellular domain of p75NTR, abolish repellent ephrinA reverse signalling in the stripe assay. This indicates that retinal cells secrete proneurotrophins, inducing the ephrinA-p75NTR interaction and enabling repellent axon guidance. The antagonistic functions of proBDNF and BDNF raise the possibility that topographic branching is controlled by local control of processing of proneurotrophins.
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