CD44 correlates with longevity and enhances basal ATF6 activity and ER stress resistance.
CD44 correlates with longevity and enhances basal ATF6 activity and ER stress resistance.
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DOI：
10.1016/j.celrep.2023.113130
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发表时间：
2023-09-26
期刊：
影响因子：
8.8
通讯作者：
中科院分区：
文献类型：
--
作者：
裸鼠是最长寿的啮齿动物，能抵抗多种与年龄相关的疾病，包括神经退行性变。然而，核磁共振抵抗神经退行性疾病的潜在机制仍然不清楚。在这里，我们从NMRS中分离出少突胶质前体细胞(OPC)，并将它们的转录组与其他哺乳动物的转录组进行了比较。细胞外基质(ECM)基因最能区分长寿和短寿物种的OPC。值得注意的是，CD44的表达水平不仅在长寿物种的OPC中高表达，而且在多种细胞类型/组织中与长寿呈正相关。CD44是一种ECM结合蛋白，被认为通过介导透明质酸(HA)的作用而有助于核磁共振长寿。我们发现CD44定位于内质网(ER)并增强ATF6的基础活性。CD44修饰内质网的蛋白质组和膜性质，并以一种依赖于未折叠的蛋白质反应调节因子的方式增强内质网应激抗性，而不需要HA。CD44在蛋白平衡调节中的HA非依赖性作用可能有助于哺乳动物的长寿。通过对短寿和长寿哺乳动物的比较转录组学，Takasugi等人。确定了长寿和CD44水平之间的相关性。CD44定位于内质网，增强基础ATF6活性和内质网抗应激能力。CD44在蛋白平衡调节中的这种非透明质酸依赖的作用可能有助于哺乳动物的长寿。
The naked mole rat (NMR) is the longest-lived rodent, resistant to multiple age-related diseases including neurodegeneration. However, the mechanisms underlying the NMR’s resistance to neurodegenerative diseases remain elusive. Here, we isolated oligodendrocyte progenitor cells (OPCs) from NMRs and compared their transcriptome with that of other mammals. Extracellular matrix (ECM) genes best distinguish OPCs of long- and short-lived species. Notably, expression levels of CD44, an ECM-binding protein that has been suggested to contribute to NMR longevity by mediating the effect of hyaluronan (HA), are not only high in OPCs of long-lived species but also positively correlate with longevity in multiple cell types/tissues. We found that CD44 localizes to the endoplasmic reticulum (ER) and enhances basal ATF6 activity. CD44 modifies proteome and membrane properties of the ER and enhances ER stress resistance in a manner dependent on unfolded protein response regulators without the requirement of HA. HA-independent role of CD44 in proteostasis regulation may contribute to mammalian longevity. Through comparative transcriptomics of short- and long-lived mammals, Takasugi et al. identified a correlation between longevity and CD44 levels. CD44 localizes to the ER and enhances basal ATF6 activity and ER stress resistance without HA. This HA-independent role of CD44 in proteostasis regulation may contribute to mammalian longevity.
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影响因子：
4.8
作者：
Pure, Ellen;Assoian, Richard K.
通讯作者：
Assoian, Richard K.
影响因子：
3.3
作者：
Katoh Y;Michisaka S;Nozaki S;Funabashi T;Hirano T;Takei R;Nakayama K
通讯作者：
Nakayama K
影响因子：
9.8
作者：
Laitman BM;Asp L;Mariani JN;Zhang J;Liu J;Sawai S;Chapouly C;Horng S;Kramer EG;Mitiku N;Loo H;Burlant N;Pedre X;Hara Y;Nudelman G;Zaslavsky E;Lee YM;Braun DA;Lu QR;Narla G;Raine CS;Friedman SL;Casaccia P;John GR
通讯作者：
John GR
DOI：
10.1016/j.bbi.2016.01.005
发表时间：
2016-10
期刊：
Brain, behavior, and immunity
影响因子：
--
作者：
Fernandez-Castaneda A;Gaultier A
通讯作者：
Gaultier A
影响因子：
7.3
作者：
Cowman MK;Lee HG;Schwertfeger KL;McCarthy JB;Turley EA
通讯作者：
Turley EA