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Nucleoskeleton dynamics and functions in health and disease

Authors Meinke P, Makarov A, Lê Thành P, Sadurska D, Schirmer E

Received 13 October 2014

Accepted for publication 12 November 2014

Published 27 January 2015 Volume 2015:7 Pages 55—69

DOI https://doi.org/10.2147/CHC.S53821

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Professor Denis Wirtz


Peter Meinke, Alexandr A Makarov, Phú Lê Thành, Daina Sadurska, Eric C Schirmer

Wellcome Trust Centre for Cell Biology and Institute of Cell Biology, University of Edinburgh, Edinburgh, UK

Abstract: It is a common misconception to view the "cyto"-skeleton as just the filament systems in the "cyto"-plasm. In fact, the cytoskeleton extends into the nucleus where the complex network connects to chromatin, and it also connects through the plasma membrane to the cytoskeleton of adjacent cells and to the "exo"-skeleton of the extracellular matrix. This review will focus principally on the subcomplex of the cytoskeleton associated with the nucleus, often referred to as the nucleoskeleton, but in the context of its extensive interconnectivity with the rest of the nucleus and with cytoplasmic filament systems all the way to the exoskeleton. The nucleoskeleton, made principally of type-V intermediate filament lamins, connects across the double membrane system of the nuclear envelope to likely all three primary cytoplasmic filament systems. It provides structural stability to the nucleus, and also incredible flexibility. In both its core structural aspect and through specificity gained by tissue-specific partner proteins, it contributes to genome organization and regulation as well as to signal transduction, both through chemical signaling cascades and likely through mechanotransduction. Defects in the nucleoskeleton have far-ranging effects due to its interactions with cytoplasmic filament systems, from mispositioning of nuclei to disruption of cell polarity and both decreased and increased cell migration depending on the defect. Accordingly, it is not surprising that many nucleoskeletal components are linked to a wide range of human diseases from specific types of cancer to muscular dystrophies, neuropathies, dermopathies, and premature aging syndromes.

Keywords: nuclear envelope, lamin, LINC complex, cytoskeleton, nuclear envelopathies

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