The cytolinker plectin regulates nuclear mechanotransduction in keratinocytes

Filipe V. Almeida, Gernot Walko, James R. McMillan, John A. McGrath, Gerhard Wiche, Asa H. Barber, John T. Connelly

研究成果: Article同行評審

39 引文 斯高帕斯(Scopus)

摘要

The transmission of mechanical forces to the nucleus is important for intracellular positioning, mitosis and cell motility, yet the contribution of specific components of the cytoskeleton to nuclear mechanotransduction remains unclear. In this study, we examine how crosstalk between the cytolinker plectin and F-actin controls keratin network organisation and the 3D nuclear morphology of keratinocytes. Using micro-patterned surfaces to precisely manipulate cell shape, we find that cell adhesion and spreading regulate the size and shape of the nucleus. Disruption of the keratin cytoskeleton through loss of plectin facilitated greater nuclear deformation, which depended on actomyosin contractility. Nuclear morphology did not depend on direct linkage of the keratin cytoskeleton with the nuclear membrane, rather loss of plectin reduced keratin filament density around the nucleus. We further demonstrate that keratinocytes have abnormal nuclear morphologies in the epidermis of plectin-deficient, epidermolysis bullosa simplex patients. Taken together, our data demonstrate that plectin is an essential regulator of nuclear morphology in vitro and in vivo and protects the nucleus from mechanical deformation.

原文English
頁(從 - 到)4475-4486
頁數12
期刊Journal of Cell Science
128
發行號24
DOIs
出版狀態Published - 2015

All Science Journal Classification (ASJC) codes

  • 細胞生物學

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