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角蛋白异构体转变在伤口愈合过程中调节运动信号。

Keratin isoform shifts modulate motility signals during wound healing.

作者信息

Nanes Benjamin A, Bhatt Kushal, Boujemaa-Paterski Rajaa, Azarova Evgenia, Munawar Sabahat, Rajendran Divya, Isogai Tadamoto, Dean Kevin M, Medalia Ohad, Danuser Gaudenz

机构信息

Department of Dermatology, UT Southwestern Medical Center; Dallas, TX 75390, USA.

Lyda Hill Department of Bioinformatics and Cecil H and Ida Green Center for Systems Biology, UT Southwestern Medical Center; Dallas, TX 75390, USA.

出版信息

bioRxiv. 2024 Apr 21:2023.05.04.538989. doi: 10.1101/2023.05.04.538989.

DOI:10.1101/2023.05.04.538989
PMID:37205459
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10187270/
Abstract

Keratin intermediate filaments form strong mechanical scaffolds that confer structural stability to epithelial tissues, but the reason this function requires a protein family with 54 isoforms is not understood. During skin wound healing, a shift in keratin isoform expression alters the composition of keratin filaments. How this change modulates cellular function to support epidermal remodeling remains unclear. We report an unexpected effect of keratin isoform variation on kinase signal transduction. Increased expression of wound-associated keratin 6A, but not of steady-state keratin 5, potentiated keratinocyte migration and wound closure without compromising epidermal stability by activating myosin motors. This pathway depended on isoform-specific interaction between intrinsically disordered keratin head domains and non-filamentous vimentin shuttling myosin-activating kinases. These results substantially expand the functional repertoire of intermediate filaments from their canonical role as mechanical scaffolds to include roles as isoform-tuned signaling scaffolds that organize signal transduction cascades in space and time to influence epithelial cell state.

摘要

角蛋白中间丝形成强大的机械支架，赋予上皮组织结构稳定性，但尚不清楚为何这种功能需要一个拥有54种异构体的蛋白质家族。在皮肤伤口愈合过程中，角蛋白异构体表达的转变会改变角蛋白丝的组成。这种变化如何调节细胞功能以支持表皮重塑仍不清楚。我们报告了角蛋白异构体变异对激酶信号转导的意外影响。伤口相关角蛋白6A而非稳态角蛋白5的表达增加，通过激活肌球蛋白马达增强了角质形成细胞的迁移和伤口闭合，而不影响表皮稳定性。该途径依赖于内在无序的角蛋白头部结构域与非丝状波形蛋白穿梭肌球蛋白激活激酶之间的异构体特异性相互作用。这些结果极大地扩展了中间丝的功能范围，从其作为机械支架的经典作用扩展到包括作为异构体调节的信号支架的作用，即在空间和时间上组织信号转导级联以影响上皮细胞状态。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/eed6322a53d9/nihpp-2023.05.04.538989v2-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/10a2638807ce/nihpp-2023.05.04.538989v2-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/6edeb4236e50/nihpp-2023.05.04.538989v2-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/849bc1b0b23d/nihpp-2023.05.04.538989v2-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/1fcce9f3446e/nihpp-2023.05.04.538989v2-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/d35534447f2f/nihpp-2023.05.04.538989v2-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/01d4d069293f/nihpp-2023.05.04.538989v2-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/eed6322a53d9/nihpp-2023.05.04.538989v2-f0007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/10a2638807ce/nihpp-2023.05.04.538989v2-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/6edeb4236e50/nihpp-2023.05.04.538989v2-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/849bc1b0b23d/nihpp-2023.05.04.538989v2-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/1fcce9f3446e/nihpp-2023.05.04.538989v2-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/d35534447f2f/nihpp-2023.05.04.538989v2-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/01d4d069293f/nihpp-2023.05.04.538989v2-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/bd68/11042586/eed6322a53d9/nihpp-2023.05.04.538989v2-f0007.jpg

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The Proteome of Hand Eczema Assessed by Tape Stripping.通过胶带撕脱法评估手部湿疹的蛋白质组学。
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Spatially resolved proteomic map shows that extracellular matrix regulates epidermal growth.
空间分辨蛋白质组图谱显示细胞外基质调节表皮生长。
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