Reduced bone morphogenic protein signaling along the gut-neuron axis by heat shock factor promotes longevity.
Reduced bone morphogenic protein signaling along the gut-neuron axis by heat shock factor promotes longevity.
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DOI：
10.1111/acel.13693
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发表时间：
2022-09
期刊：
影响因子：
7.8
通讯作者：
Douglas, Peter M.
中科院分区：
文献类型：
--
作者：
Arneaud, Sonja L. B.;McClendon, Jacob;Tatge, Lexus;Watterson, Abigail;Zuurbier, Kielen R.;Madhu, Bhoomi;Gumienny, Tina L.;Douglas, Peter M.
衰老是一个复杂的和高度调节的相互交织的信号机制的过程。作为一种古老的热适应和蛋白质稳态的转录调节因子，热休克因子（HSF-1）在神经系统中进化出控制年龄进展的功能;然而，HSF-1调节组织年龄的分子细节和信号动力学仍然不清楚。在此，我们报告了秀丽隐杆线虫神经系统中HSF-1的非自主性年龄调节模式，该模式通过骨形态发生蛋白BMP信号通路调节外周组织中的膜运输。特别是，HSF-1抑制神经元特异性BMP配体DBL-1的表达，并在肠道内启动互补的负反馈回路。SMAD转录辅激活因子SMA-3通过减少外周中DBL-1的接收，抑制关键膜运输调节因子的表达，包括参与早期（RAB-5）、晚期（RAB-7）和再循环（RAB-11.1）内体动力学的Rab GTP酶和BMP受体结合蛋白SMA-10。这减少了肠中I型BMP受体SMA-6的细胞表面驻留和稳态水平，并进一步抑制了向外周的信号传输。因此，HSF-1协调BMP信号沿着肠-脑轴的能力是年龄进展的重要决定因素。通过神经hsf-1减少DBL-1/BMP信号传导，通过抑制膜运输机制减少专用DBL-1受体SMA-6的细胞表面驻留，促进肠道中的负反馈回路。
Aging is a complex and highly regulated process of interwoven signaling mechanisms. As an ancient transcriptional regulator of thermal adaptation and protein homeostasis, the Heat Shock Factor, HSF‐1, has evolved functions within the nervous system to control age progression; however, the molecular details and signaling dynamics by which HSF‐1 modulates age across tissues remain unclear. Herein, we report a nonautonomous mode of age regulation by HSF‐1 in the Caenorhabditis elegans nervous system that works through the bone morphogenic protein, BMP, signaling pathway to modulate membrane trafficking in peripheral tissues. In particular, HSF‐1 represses the expression of the neuron‐specific BMP ligand, DBL‐1, and initiates a complementary negative feedback loop within the intestine. By reducing receipt of DBL‐1 in the periphery, the SMAD transcriptional coactivator, SMA‐3, represses the expression of critical membrane trafficking regulators including Rab GTPases involved in early (RAB‐5), late (RAB‐7), and recycling (RAB‐11.1) endosomal dynamics and the BMP receptor binding protein, SMA‐10. This reduces cell surface residency and steady‐state levels of the type I BMP receptor, SMA‐6, in the intestine and further dampens signal transmission to the periphery. Thus, the ability of HSF‐1 to coordinate BMP signaling along the gut–brain axis is an important determinate in age progression. Reduced DBL‐1/BMP signaling by neural hsf‐1 promotes a negative feedback loop in the intestine by reducing cell surface residency of the dedicated DBL‐1 receptor, SMA‐6, via the repression of membrane trafficking machinery.
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影响因子：
--
作者：
Kumar N;Jain V;Singh A;Jagtap U;Verma S;Mukhopadhyay A
通讯作者：
Mukhopadhyay A
影响因子：
16
作者：
Labbadia J;Morimoto RI
通讯作者：
Morimoto RI
DOI：
10.1534/g3.117.300416
发表时间：
2018-01-04
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Clark JF;Meade M;Ranepura G;Hall DH;Savage-Dunn C
通讯作者：
Savage-Dunn C
影响因子：
11.8
作者：
Egge, Nathan;Arneaud, Sonja L. B.;Douglas, Peter M.
通讯作者：
Douglas, Peter M.
影响因子：
14.9
作者：
Bailey TL;Johnson J;Grant CE;Noble WS
通讯作者：
Noble WS