一种由转录调节因子 P53 的细胞质作用控制的感觉轴突退化的顺行途径。
An anterograde pathway for sensory axon degeneration gated by a cytoplasmic action of the transcriptional regulator P53.
机构信息
Laboratory of Brain Development and Repair, Rockefeller University, New York, NY 10065, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA; Department of Biochemistry, Weill Cornell Medical College, New York, NY 10065, USA.
Laboratory of Brain Development and Repair, Rockefeller University, New York, NY 10065, USA; Department of Biology, Stanford University, Stanford, CA 94305, USA.
出版信息
Dev Cell. 2021 Apr 5;56(7):976-984.e3. doi: 10.1016/j.devcel.2021.03.011.
Axon remodeling through sprouting and pruning contributes to the refinement of developing neural circuits. A prominent example is the pruning of developing sensory axons deprived of neurotrophic support, which is mediated by a caspase-dependent (apoptotic) degeneration process. Distal sensory axons possess a latent apoptotic pathway, but a cell body-derived signal that travels anterogradely down the axon is required for pathway activation. The signaling mechanisms that underlie this anterograde process are poorly understood. Here, we show that the tumor suppressor P53 is required for anterograde signaling. Interestingly loss of P53 blocks axonal but not somatic (i.e., cell body) caspase activation. Unexpectedly, P53 does not appear to have an acute transcriptional role in this process and instead appears to act in the cytoplasm to directly activate the mitochondrial apoptotic pathway in axons. Our data support the operation of a cytoplasmic role for P53 in the anterograde death of developing sensory axons.
通过发芽和修剪来重塑轴突有助于发育中的神经回路的精细化。一个突出的例子是发育中的感觉轴突在缺乏神经营养支持时的修剪，这是由半胱天冬酶依赖性（凋亡）退化过程介导的。远端感觉轴突具有潜在的凋亡途径，但需要源自细胞体的信号沿着轴突逆行传播才能激活途径。这种逆行过程的信号机制知之甚少。在这里，我们表明肿瘤抑制因子 P53 是逆行信号所必需的。有趣的是，P53 的缺失会阻断轴突但不会阻断体细胞（即细胞体）半胱天冬酶的激活。出人意料的是，P53 似乎在这个过程中没有急性转录作用，而是在细胞质中直接激活轴突中的线粒体凋亡途径。我们的数据支持 P53 在发育中的感觉轴突逆行死亡中的细胞质作用的运作。
Zotero 插件