Morphological abnormalities of the bounding membranes of the nucleus have long been associated with human diseases from cancer to premature aging to neurodegeneration. Studies over the past few decades support that there are both cell intrinsic and extrinsic factors (e.g. mechanical force) that can lead to nuclear envelope ‘herniations’, a broad catch-all term that reveals little about the underlying molecular mechanisms that contribute to these morphological defects. While there are many genetic perturbations that could ultimately change nuclear shape, here, we focus on a subset of nuclear envelope herniations that likely arise as a consequence of disrupting physiological nuclear membrane remodeling pathways required to maintain nuclear envelope homeostasis. For example, stalling of the interphase nuclear pore complex (NPC) biogenesis pathway and/or triggering of NPC quality control mechanisms can lead to herniations in budding yeast, which are remarkably similar to those observed in human disease models of early-onset dystonia. By also examining the provenance of nuclear envelope herniations associated with emerging nuclear autophagy and nuclear egress pathways, we will provide a framework to help understand the molecular pathways that contribute to nuclear deformation.
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Cover Image
Cover Image
The image represents a simplified ‘open’ cell of the gram-positive bacterium Streptomyces coelicolor and selected components of its zinc metabolism. The zinc sensor protein – zinc uptake regulator (Zur) – is shown in metallic blue in the middle, bound to DNA (green) where it works as a transcriptional repressor when zinc levels are adequate. The Zur-regulated high-affinity zinc uptake system ZnuABC is shown in purple. Synthesis of the secreted zincophore coelibactin is also Zur-regulated. Zinc ions are shown as silver balls surrounding the cell, and bound to Zur; for details see pages 983–1001.
The image has been created by Alevtina Mikhaylina with the help of Claudia A. Blindauer and David J. Scanlan.
Fantastic nuclear envelope herniations and where to find them
David J. Thaller, C. Patrick Lusk; Fantastic nuclear envelope herniations and where to find them. Biochem Soc Trans 20 August 2018; 46 (4): 877–889. doi: https://doi.org/10.1042/BST20170442
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