Nuclear Shape, Mechanics, and Mechanotransduction
- 6 June 2008
- journal article
- review article
- Published by Ovid Technologies (Wolters Kluwer Health) in Circulation Research
- Vol. 102 (11), 1307-1318
- https://doi.org/10.1161/circresaha.108.173989
Abstract
In eukaryotic cells, the nucleus contains the genome and is the site of transcriptional regulation. The nucleus is the largest and stiffest organelle and is exposed to mechanical forces transmitted through the cytoskeleton from outside the cell and from force generation within the cell. Here, we discuss the effect of intra- and extracellular forces on nuclear shape and structure and how these force-induced changes could be implicated in nuclear mechanotransduction, ie, force-induced changes in cell signaling and gene transcription. We review mechanical studies of the nucleus and nuclear structural proteins, such as lamins. Dramatic changes in nuclear shape, organization, and stiffness are seen in cells where lamin proteins are mutated or absent, as in genetically engineered mice, RNA interference studies, or human disease. We examine the different mechanical pathways from the force-responsive cytoskeleton to the nucleus. We also highlight studies that link changes in nuclear shape with cell function during developmental, physiological, and pathological modifications. Together, these studies suggest that the nucleus itself may play an important role in the response of the cell to force.Keywords
This publication has 157 references indexed in Scilit:
- Lamin A/C haploinsufficiency causes dilated cardiomyopathy and apoptosis-triggered cardiac conduction system diseaseJournal of Molecular and Cellular Cardiology, 2008
- Identification of differentially expressed proteins in ovarian cancer using high-density protein microarraysProceedings of the National Academy of Sciences, 2007
- Physical plasticity of the nucleus in stem cell differentiationProceedings of the National Academy of Sciences, 2007
- An in vitro nuclear disassembly system reveals a role for the RanGTPase system and microtubule-dependent steps in nuclear envelope breakdownThe Journal of cell biology, 2007
- Mouse models of the laminopathiesExperimental Cell Research, 2007
- “Laminopathies”: A wide spectrum of human diseasesExperimental Cell Research, 2007
- p53 targets identified by protein expression profilingProceedings of the National Academy of Sciences, 2007
- Distinct structural and mechanical properties of the nuclear lamina in Hutchinson–Gilford progeria syndromeProceedings of the National Academy of Sciences of the United States of America, 2006
- Mutant nuclear lamin A leads to progressive alterations of epigenetic control in premature agingProceedings of the National Academy of Sciences, 2006
- Local force and geometry sensing regulate cell functionsNature Reviews Molecular Cell Biology, 2006