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Mechanisms and functions of nuclear envelope remodelling

Nature Reviews Molecular Cell Biology volume 18, pages 229–245 (2017)Cite this article

Subjects

Key Points

  • The organization of the nuclear envelope (NE) is perfectly adapted to its function as a compartment boundary and protective coat for the genome.

  • The plasticity of the NE allows it to withstand considerable mechanical challenges, whether cells are embedded within tissues or during migration. In the case of NE rupture, membrane lesions are rapidly repaired to avoid genome damage.

  • Local NE remodelling is required for the biogenesis of nuclear pore complexes, the nuclear egress of large particles such as ribonucleoprotein complexes or certain viruses and the elimination of defective NE components.

  • Distinct modes of NE re-organization evolved for the process of nuclear division, of which the complete disassembly and reassembly of the NE during open mitosis represents an extreme case.

  • Changes in NE composition and morphology accompany differentiation and contribute to tissue-specific cell function.

Abstract

As a compartment border, the nuclear envelope (NE) needs to serve as both a protective membrane shell for the genome and a versatile communication interface between the nucleus and the cytoplasm. Despite its important structural role in sheltering the genome, the NE is a dynamic and highly adaptable boundary that changes composition during differentiation, deforms in response to mechanical challenges, can be repaired upon rupture and even rapidly disassembles and reforms during open mitosis. NE remodelling is fundamentally involved in cell growth, division and differentiation, and if perturbed can lead to devastating diseases such as muscular dystrophies or premature ageing.

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Figure 1: Nuclear envelope architecture and the integration of new components.
Figure 2: Nuclear envelope remodelling in response to mechanical cues and rupture.
Figure 3: Mechanisms governing nuclear envelope breakdown and reassembly in animal cells undergoing open mitosis.
Figure 4: Nuclear egress of herpesviruses.
Figure 5: Nuclear envelope remodelling during cell differentiation.

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Acknowledgements

The authors apologize for not citing all primary literature owing to space limitations. The authors thank L. Champion, K. Frischer-Ordu and L. Bammert for critical reading of the manuscript, the ETH Zurich and the Swiss National Science Foundation for continuous financial support and the ERC for funding NE research in the Kutay laboratory by the ERC Advanced Grant NucEnv to U.K.

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  1. Institute of Biochemistry, ETH Zurich, Otto-Stern-Weg 3, Zurich, 8093, Switzerland

    Rosemarie Ungricht & Ulrike Kutay

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  1. Rosemarie Ungricht
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  2. Ulrike Kutay
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Correspondence to Ulrike Kutay.

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DATABASES

Electron Microscopy Data Bank

Glossary

Ribonucleoprotein complexes

(RNP complexes). Large complexes composed of RNA and proteins, which are involved in a wide range of cellular processes such as translation, RNA processing and telomere function.

Perinuclear space

The lumen enclosed by the inner and outer nuclear membranes that is continuous with the lumen of the endoplasmic reticulum.

Amphipathic helix

An -helix that contains hydrophobic and polar amino acid side chains on its opposing faces.

Autophagy

A lysosome-based degradation pathway for the destruction and recycling of cellular material.

Endoplasmic reticulum-associated degradation

(ERAD). A cellular quality-control pathway that targets misfolded proteins of the ER for ubiquitylation and subsequent degradation by the proteasome in the cytosol.

RING finger

(Really interesting new gene finger). A specialized zinc-binding protein domain of 40–60 amino acids that mediates protein–protein interactions of factors involved in protein ubiquitylation.

F-Box proteins

Proteins that contain a structural motif of approximately 50 amino acids called the F-box. They were first identified as substrate-specific adaptors of E3 ubiquitin ligase complexes that contain cullin1 and SKP1 (to collectively form the SCF complex).

Retinoic acid receptor

A member of the nuclear receptor family of transcription factors that is activated by the binding of retinoic acid. It binds to retinoic acid-responsive elements as a heterodimer with a retinoic X receptor.

ESCRT-III

(Endosomal sorting complex required for transport-III). An assembly of filamentous proteins that form spiral- shaped structures within annular membrane holes and mediate membrane scission, which results in the closure of membrane pores.

Spindle pole bodies

(SPBs). The microtubule-organizing centres in yeast that are functionally equivalent to the centrosomes in higher eukaryotes.

Semi-open mitosis

A form of mitosis in which the nuclear envelope is partially dismantled, accompanied by increased nuclear envelope permeability.

Cyclin-dependent kinase 1

(CDK1). A member of the family of cyclin-dependent protein kinases that are functionalized by complex formation with a cyclin protein. CDK1 in complex with cyclin B promotes entry into mitosis in mammalian cells.

Lipin

A member of the family of phosphatidate phosphatases that converts phosphatidic acid into diacylglycerol (DAG), which can be used for the production of storage lipids or structural phospholipids.

LAP2, emerin, MAN1 domain

(LEM domain). A bi-helical structural module found in the nucleoplasmic domain of some INM and nuclear proteins that mediates interaction with barrier-to-autointegration factor (BAF).

Barrier-to-autointegration factor

(BAF). A homodimeric DNA-binding protein that directly interacts with members of the LEM domain protein family.

Aurora kinase B

A member of the Aurora family of Ser/Thr kinases. A component of the chromosomal passenger complex that orchestrates several distinct steps of mitosis, including the fidelity of spindle assembly and cytokinesis.

Nucleosomes

The fundamental packing units of chromatin, which comprise a segment of DNA and a core histone octamer.

Importins

RAN·GTP-binding nuclear transport receptors that recognize nuclear localization signals (NLSs) and mediate passage of NLS-containing proteins through nuclear pore complexes.

RAN·GTP

GTP-bound form of the small GTPase RAS-related nuclear protein (RAN) that confers directionality to nucleocytoplasmic transport. A high concentration of nuclear RAN·GTP, which is maintained by the chromatin-bound RAN guanine nucleotide exchange factor, facilitates unloading of transport cargo from importins in the nucleus.

Annulate lamellae

Stacks of endoplasmic reticulum membrane sheets that contain nuclear pore complexes.

Nucleoplasmic reticulation

Nuclear envelope-derived membrane invaginations, tubules or reticular structures that project into or traverse the nucleoplasm.

AAA-ATPase

(ATPases associated with diverse cellular activities-ATPase). A protein family defined by a structurally conserved ATPase domain that assembles into oligomeric rings. ATP hydrolysis is used to power the conformational remodelling of macromolecules.

Nuclear egress

An unusual vesicular transport pathway across the nuclear envelope that is used for nuclear export of herpesvirus particles.

Torsin family

A family of AAA-ATPases that reside in the ER lumen and the contiguous perinuclear space. An amino acid deletion in torsin 1A (TOR1A), TOR1AE, causes a severe movement disorder, early-onset dystonia.

RB

(Retinoblastoma protein). A tumour suppressor protein that inhibits cell cycle progression in its hypophosphorylated form.

MYOD

(Myoblast determination protein). A myogenic transcription factor and early marker for myogenic commitment.

Acrosome

A Golgi-derived intracellular organelle that is positioned on top of the anterior half of the sperm head.

Manchette

A transient structure built by microtubule bundles that surrounds the posterior part of the nucleus in the developing sperm head.

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Ungricht, R., Kutay, U. Mechanisms and functions of nuclear envelope remodelling. Nat Rev Mol Cell Biol 18, 229–245 (2017). https://doi.org/10.1038/nrm.2016.153

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