Orchestrated control of filaggrin-actin scaffolds underpins cornification.
Orchestrated control of filaggrin-actin scaffolds underpins cornification.
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DOI：
10.1038/s41419-018-0407-2
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发表时间：
2018-04-01
影响因子：
9
通讯作者：
Ogg GS
中科院分区：
文献类型：
--
作者：
Gutowska-Owsiak D;de La Serna JB;Fritzsche M;Naeem A;Podobas EI;Leeming M;Colin-York H;O'Shaughnessy R;Eggeling C;Ogg GS
表皮分层主要取决于角质形成细胞的分化和角化导致的程序性死亡，从而形成保护性皮肤屏障。角化是动态控制的蛋白质聚丝蛋白，快速释放的透明角质颗粒（KHG）。然而，角化的机制在很大程度上仍然是难以捉摸的，部分原因是用于研究角化细胞中的聚丝蛋白组织的观察技术的局限性。此外，虽然KHG中角蛋白的丰度已得到很好的描述，但不清楚肌动蛋白是否也有助于它们的形成或命运。我们采用先进的（超分辨率）显微镜检查在分化过程中的皮肤和人角质形成细胞中的聚丝蛋白组织和动力学。我们发现，聚丝蛋白的组织依赖于细胞质肌动蛋白细胞骨架，包括α-和β-肌动蛋白支架的作用。在分化过程中，含微丝蛋白的KHG表现出高迁移率并向细胞核迁移。针对肌动蛋白网络的药理学破坏导致颗粒崩解和加速角化。我们确定了AKT丝氨酸/苏氨酸激酶1（AKT 1）的作用，它控制热休克蛋白B1（HspB 1）的结合偏好和功能，促进从肌动蛋白稳定化到聚丝蛋白加工的转换。我们的研究结果表明，角化的扩展模型中，丝聚蛋白利用肌动蛋白，以有效地控制角质形成细胞的分化和死亡，促进表皮分层和形成一个功能齐全的皮肤屏障。
Epidermal stratification critically depends on keratinocyte differentiation and programmed death by cornification, leading to formation of a protective skin barrier. Cornification is dynamically controlled by the protein filaggrin, rapidly released from keratohyalin granules (KHGs). However, the mechanisms of cornification largely remain elusive, partly due to limitations of the observation techniques employed to study filaggrin organization in keratinocytes. Moreover, while the abundance of keratins within KHGs has been well described, it is not clear whether actin also contributes to their formation or fate. We employed advanced (super-resolution) microscopy to examine filaggrin organization and dynamics in skin and human keratinocytes during differentiation. We found that filaggrin organization depends on the cytoplasmic actin cytoskeleton, including the role for α- and β-actin scaffolds. Filaggrin-containing KHGs displayed high mobility and migrated toward the nucleus during differentiation. Pharmacological disruption targeting actin networks resulted in granule disintegration and accelerated cornification. We identified the role of AKT serine/threonine kinase 1 (AKT1), which controls binding preference and function of heat shock protein B1 (HspB1), facilitating the switch from actin stabilization to filaggrin processing. Our results suggest an extended model of cornification in which filaggrin utilizes actins to effectively control keratinocyte differentiation and death, promoting epidermal stratification and formation of a fully functional skin barrier.
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DOI：
10.1016/j.jaci.2011.01.031
发表时间：
2011-03
期刊：
The Journal of allergy and clinical immunology
影响因子：
--
作者：
Brown SJ;Asai Y;Cordell HJ;Campbell LE;Zhao Y;Liao H;Northstone K;Henderson J;Alizadehfar R;Ben-Shoshan M;Morgan K;Roberts G;Masthoff LJ;Pasmans SG;van den Akker PC;Wijmenga C;Hourihane JO;Palmer CN;Lack G;Clarke A;Hull PR;Irvine AD;McLean WH
通讯作者：
McLean WH
影响因子：
5.3
作者：
LAVOIE, JN;LAMBERT, H;LANDRY, J
通讯作者：
LANDRY, J
影响因子：
4.8
作者：
Kamata, Yayoi;Taniguchi, Aya;Takeda, Atsushi
通讯作者：
Takeda, Atsushi
影响因子：
30.8
作者：
Cookson, WOCM;Ubhi, B;Harper, JI
通讯作者：
Harper, JI
影响因子：
3
作者：
GUNZEL, S;WEIDENTHALER, B;ANTONLAMPRECHT, I
通讯作者：
ANTONLAMPRECHT, I