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

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Abstract

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 acto-myosin 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.
Original languageEnglish
Pages (from-to)4475-4486
Number of pages12
JournalJournal of Cell Science
Volume128
Issue number24
DOIs
Publication statusPublished - 15 Dec 2015

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Plectin
Keratinocytes
Keratins
Cytoskeleton
pioglitazone
Epidermolysis Bullosa Simplex
Cell Shape
Nuclear Envelope
Myosins
Mitosis
Epidermis
Cell Adhesion
Cell Movement
Actins

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Almeida, F. V., Walko, G., McMillan, J. R., McGrath, J. A., Wiche, G., Barber, A. H., & Connelly, J. T. (2015). The cytolinker plectin regulates nuclear mechanotransduction in keratinocytes. Journal of Cell Science, 128(24), 4475-4486. https://doi.org/10.1242/jcs.173435

The cytolinker plectin regulates nuclear mechanotransduction in keratinocytes. / Almeida, Filipe V; Walko, Gernot; McMillan, James R; McGrath, John A; Wiche, Gerhard; Barber, Asa H; Connelly, John T.

In: Journal of Cell Science, Vol. 128, No. 24, 15.12.2015, p. 4475-4486.

Research output: Contribution to journalArticle

Almeida, FV, Walko, G, McMillan, JR, McGrath, JA, Wiche, G, Barber, AH & Connelly, JT 2015, 'The cytolinker plectin regulates nuclear mechanotransduction in keratinocytes', Journal of Cell Science, vol. 128, no. 24, pp. 4475-4486. https://doi.org/10.1242/jcs.173435
Almeida FV, Walko G, McMillan JR, McGrath JA, Wiche G, Barber AH et al. The cytolinker plectin regulates nuclear mechanotransduction in keratinocytes. Journal of Cell Science. 2015 Dec 15;128(24):4475-4486. https://doi.org/10.1242/jcs.173435
Almeida, Filipe V ; Walko, Gernot ; McMillan, James R ; McGrath, John A ; Wiche, Gerhard ; Barber, Asa H ; Connelly, John T. / The cytolinker plectin regulates nuclear mechanotransduction in keratinocytes. In: Journal of Cell Science. 2015 ; Vol. 128, No. 24. pp. 4475-4486.
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