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非洲爪蟾p75神经营养因子受体(p75(NTR))的表达与功能表明发育调控机制的进化。

Expression and function of Xenopus laevis p75(NTR) suggest evolution of developmental regulatory mechanisms.

作者信息

Hutson L D, Bothwell M

机构信息

Department of Physiology and Biophysics, University of Washington, Seattle, WA 98195, USA.

出版信息

J Neurobiol. 2001 Nov 5;49(2):79-98. doi: 10.1002/neu.1067.

Abstract

Neurotrophins signal through two different classes of receptors, members of the trk family of receptor tyrosine kinases, and p75 neurotrophin receptor (p75(NTR)), a member of the tumor necrosis factor receptor family. While neurotrophin binding to trks results in, among other things, increased cell survival, p75(NTR) has enigmatically been implicated in promoting both survival and cell death. Which of these two signals p75(NTR) imparts depends on the specific cellular context. Xenopus laevis is an excellent system in which to study p75(NTR) function in vivo because of its amenability to experimental manipulation. We therefore cloned partial cDNAs of two p75(NTR) genes from Xenopus, which we have termed p75(NTR)a and p75(NTR)b. We then cloned two different cDNAs, both of which encompass the full coding region of p75(NTR)a. Early in development both p75(NTR)a and p75(NTR)b are expressed in developing cranial ganglia and presumptive spinal sensory neurons, similar to what is observed in other species. Later, p75(NTR)a expression largely continues to parallel p75(NTR) expression in other species. However, Xenopus p75(NTR)a is additionally expressed in the neuroepithelium of the anterior telencephalon, all layers of the retina including the photoreceptor layer, and functioning axial skeletal muscle. Finally, misexpression of full length p75(NTR) and each of two truncated mutants in developing retina reveal that p75(NTR) probably signals for cell survival in this system. This result contrasts with the reported role of p75(NTR) in developing retinae of other species, and the possible implications of this difference are discussed.

摘要

神经营养因子通过两类不同的受体发出信号,即受体酪氨酸激酶trk家族的成员,以及肿瘤坏死因子受体家族的成员p75神经营养因子受体(p75(NTR))。神经营养因子与trk结合除了会带来其他结果外,还会增加细胞存活,而p75(NTR)却神秘地与促进存活和细胞死亡都有关联。p75(NTR)传递这两种信号中的哪一种取决于特定的细胞环境。非洲爪蟾是研究p75(NTR)体内功能的绝佳系统,因为它易于进行实验操作。因此,我们从非洲爪蟾中克隆了两个p75(NTR)基因的部分cDNA,我们将其命名为p75(NTR)a和p75(NTR)b。然后我们克隆了两个不同的cDNA,它们都包含p75(NTR)a的完整编码区。在发育早期,p75(NTR)a和p75(NTR)b都在发育中的脑神经节和假定的脊髓感觉神经元中表达,这与在其他物种中观察到的情况相似。后来,p75(NTR)a的表达在很大程度上继续与其他物种中p75(NTR)的表达平行。然而,非洲爪蟾的p75(NTR)a还在前脑的神经上皮、包括感光层在内的视网膜各层以及起作用的轴向骨骼肌中表达。最后,在发育中的视网膜中全长p75(NTR)以及两个截短突变体各自的错误表达表明,p75(NTR)在这个系统中可能是细胞存活的信号。这一结果与p75(NTR)在其他物种发育中的视网膜中所报道的作用形成对比,并讨论了这种差异可能带来的影响。

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