An anterograde pathway for sensory axon degeneration gated by a cytoplasmic action of the transcriptional regulator P53.
An anterograde pathway for sensory axon degeneration gated by a cytoplasmic action of the transcriptional regulator P53.
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DOI：
10.1016/j.devcel.2021.03.011
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发表时间：
2021-04-05
影响因子：
11.8
通讯作者：
Tessier-Lavigne M
中科院分区：
文献类型：
--
作者：
Simon DJ;Belsky DM;Bowen ME;Ohn CYJ;O'Rourke MK;Shen R;Kim G;Pitts J;Attardi LD;Tessier-Lavigne M
轴突通过发芽和修剪重塑有助于发育中的神经回路的完善。一个突出的例子是修剪发展中的感觉轴突剥夺神经营养支持，这是介导的半胱天冬酶依赖性（凋亡）变性过程。远端感觉轴突具有潜在的凋亡途径，但细胞体来源的信号，顺行轴突是必要的途径激活。这种顺行过程的信号机制知之甚少。在这里，我们表明，肿瘤抑制蛋白P53是所需的顺行信号。有趣的是，P53的缺失阻断了轴突而不是体细胞（即，细胞体）半胱天冬酶激活。出乎意料的是，P53似乎在该过程中没有急性转录作用，而是似乎在细胞质中起作用，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的顺行性死亡中的细胞质作用。发育中的胚胎感觉轴突的存活受靶源性神经营养因子的水平控制。Simon等报道转录调节因子P53非常规地控制这些轴突的死亡，在细胞质中而不是细胞核中起作用，以激活线粒体凋亡途径。
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. The survival of developing embryonic sensory axons is controlled by the level of target-derived neurotrophins. Simon et al. report that the transcriptional regulator P53 controls the death of these axons non-canonically, acting in the cytoplasm, not the nucleus, to activate the mitochondrial apoptotic pathway.
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影响因子：
30.8
作者：
Dumont, P;Leu, JIJ;Murphy, M
通讯作者：
Murphy, M
影响因子：
50.3
作者：
Mello SS;Valente LJ;Raj N;Seoane JA;Flowers BM;McClendon J;Bieging-Rolett KT;Lee J;Ivanochko D;Kozak MM;Chang DT;Longacre TA;Koong AC;Arrowsmith CH;Kim SK;Vogel H;Wood LD;Hruban RH;Curtis C;Attardi LD
通讯作者：
Attardi LD
DOI：
10.1523/jneurosci.3347-10.2011
发表时间：
2011-02-02
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Courchesne SL;Karch C;Pazyra-Murphy MF;Segal RA
通讯作者：
Segal RA
影响因子：
64.8
作者：
Green, Douglas R.;Kroemer, Guido
通讯作者：
Kroemer, Guido
影响因子：
16
作者：
Follis AV;Llambi F;Merritt P;Chipuk JE;Green DR;Kriwacki RW
通讯作者：
Kriwacki RW