Sorting nuclear membrane proteins at mitosis

doi:10.1016/S0962-8924(99)01697-9

Trends in Cell Biology

Volume 10, Issue 1, 1 January 2000, Pages 5-8

https://doi.org/10.1016/S0962-8924(99)01697-9 Get rights and content

Abstract

The nuclear envelope (NE) breaks down reversibly and reassembles at mitosis. Two models of mitotic nuclear membrane disassembly and reformation have emerged from studies of NE dynamics in somatic cells and egg extracts. One model suggests that nuclear membranes fragment reversibly by vesiculation, producing NE-derived vesicles separate from the endoplasmic reticulum. The second model proposes that nuclear membranes vanish by diffusion of their integral proteins through a continuous endoplasmic reticulum. Here, we discuss critically the grounds for the elaboration of these apparently mutually exclusive views. Our conclusions favour a model in which nuclear membranes do not vesiculate during mitosis.

Section snippets

Mitotic nuclear disassembly and reassembly in somatic cells

Several observations and hypotheses have lent support to the model of nuclear membrane disassembly by vesiculation. First, ultrastructural analyses have shown that nuclear membranes break down at mitosis by progressive fragmentation, giving the impression of a random scission process¹. Second, studies of intracellular membrane trafficking led to the proposal that, as with the Golgi and the ER, the structure of the NE represents a balance between scission and fusion activities². During mitosis,

Egg extracts: a different world

A large amount of information on the assembly of nuclear membranes has originated from the use of cell-free extracts derived notably from eggs of Xenopus or sea urchin, and Drosophila embryos¹⁰. Overall, these studies promote a pathway of nuclear membrane reassembly by chromatin-targeting, binding and fusion of ‘nuclear membrane vesicles’.

Data obtained from egg reconstitution assays and from somatic cell studies have often been combined to present a unified model of NE reassembly. However, eggs

A nonuniform distribution of nuclear membrane proteins within the mitotic ER?

Increasing evidence obtained by direct localization of membrane markers in intact somatic cells indicates clearly that, during mitosis, integral proteins of nuclear membranes diffuse throughout the ER, which remains as an intact tubular cisternal network in many cell types¹ (Fig. 2b). This largely favours a model in which nuclear membranes do not vesiculate during mitosis. Whether proteins derived from a particular membrane domain disperse fully (Fig. 2b; random diffusion model) or remain

Acknowledgements

We apologize to colleagues whose work was not cited directly owing to space limitations. We thank H. Worman, J. Ellenberg, M. Terasaki and T. Rapoport for comments and sharing unpublished information. Financial support from the Association pour la Recherche contre le Cancer (J-C.C.) and from the Norwegian Research Council and the Norwegian Cancer Society (P.C.) is acknowledged.

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Cited by (53)

Nuclear Reformation at the End of Mitosis
2016, Journal of Molecular Biology
Citation Excerpt :
For example, during breakage of the eggs, the ER network fragments and forms vesicles. These vesicles bind to chromatin and fuse to a closed NE upon chromatin incubation in egg extracts, which has been misinterpreted as proof for the existence of membrane vesicles as source of the NE during nuclear reformation at the end of mitosis (for discussion, see Ref. [8]). In this review, we will also attempt to point out where results from in vitro experiments should be taken with a grain of skepticism and would benefit from confirmation in living cells.
Cells have developed highly sophisticated ways to accurately pass on their genetic information to the daughter cells. In animal cells, which undergo open mitosis, the nuclear envelope breaks down at the beginning of mitosis and the chromatin massively condenses to be captured and segregated by the mitotic spindle. These events have to be reverted in order to allow the reformation of a nucleus competent for DNA transcription and replication, as well as all other nuclear processes occurring in interphase. Here, we summarize our current knowledge of how, in animal cells, the highly compacted mitotic chromosomes are decondensed at the end of mitosis and how a nuclear envelope, including functional nuclear pore complexes, reassembles around these decondensing chromosomes.
Biology and Biophysics of the Nuclear Pore Complex and Its Components
2008, International Review of Cell and Molecular Biology
Citation Excerpt :
Whether differing results are due to the timing of detection within mitosis or to the specific isoforms detected or to some technical issue is not clear. There is independent evidence from HeLa cells for distinct vesicle populations (Chaudhary and Courvalin, 1993); however, an alternate interpretation is that such vesicles are derived artificially from microdomains within a contiguous ER‐like network (Collas and Courvalin, 2000). Studies using nuclei reconstituted in Xenopus egg extract have implicated the coatomer complex, COPI, in nuclear disassembly (Cotter et al., 2007; Liu et al., 2003; Prunuske et al., 2006).
Nucleocytoplasmic exchange of proteins and ribonucleoprotein particles occurs via nuclear pore complexes (NPCs) that reside in the double membrane of the nuclear envelope (NE). Significant progress has been made during the past few years in obtaining better structural resolution of the three‐dimensional architecture of NPC with the help of cryo‐electron tomography and atomic structures of domains from nuclear pore proteins (nucleoporins). Biophysical and imaging approaches have helped elucidate how nucleoporins act as a selective barrier in nucleocytoplasmic transport. Nucleoporins act not only in trafficking of macromolecules but also in proper microtubule attachment to kinetochores, in the regulation of gene expression and signaling events associated with, for example, innate and adaptive immunity, development and neurodegenerative disorders. Recent research has also been focused on the dynamic processes of NPC assembly and disassembly that occur with each cell cycle. Here we review emerging results aimed at understanding the molecular arrangement of the NPC and how it is achieved, defining the roles of individual nucleoporins both at the NPC and at other sites within the cell, and finally deciphering how the NPC serves as both a barrier and a conduit of active transport.
The nuclear envelope: Form and reformation
2006, Current Opinion in Cell Biology
The membrane system that encloses genomic DNA is referred to as the nuclear envelope. However, with emerging roles in signaling and gene expression, these membranes clearly serve as more than just a physical barrier separating the nucleus and cytoplasm. Recent progress in our understanding of nuclear envelope architecture and composition has also revealed an intriguing connection between constituents of the nuclear envelope and human disease, providing further impetus to decipher this cellular structure and the dramatic remodeling process it undergoes with each cell division.
Matrix metalloproteinase-1 associates with intracellular organelles and confers resistance to lamin A/C Degradation during apoptosis
2005, American Journal of Pathology
Citation Excerpt :
Important proteins of the nuclear envelope are the lamins, which are type V intermediate filament proteins arranged into a meshwork that maintains nuclear envelope integrity and organization of the interface chromatin.36 Although it has been shown that during apoptosis the lamin network is degraded by proteolytic enzymes known as caspases, very little is known about the sequence of events that take place during lamin proteolysis.31 Due to the intracellular localization of MMP-1 on the mitochondrial surface, we investigated whether this enzyme may potentially be involved in the degradation of lamins.
Since the first description of matrix metalloproteinase (MMP)-1 as an interstitial collagenase, great importance has been ascribed to this enzyme in extracellular matrix remodeling during tumoral, inflammatory, and angiogenic processes. As more evidence for the role of MMPs in targeting nonmatrix substrates emerges, casual observations that intracellular MMP-1 is found in vitro and in vivo prompt investigation of the role that MMP-1 may play on basic cell functions such as cell division and apoptosis. Here we show for the first time that MMP-1 not only has extracellular functions but that it is strongly associated with mitochondria and nuclei and accumulates within the cells during the mitotic phase of the cell cycle. On induction of apoptosis, MMP-1 co-localized with aggregated mitochondria and accumulated around fragmented nuclei. Inhibition of this enzyme by RNA interference or treatment with a broad MMP inhibitor caused faster degradation of lamin A, activation of caspases, and fragmentation of DNA when compared with untreated cells. These observations strongly suggest that intracellular association of MMP-1 to mitochondria and nuclei confers resistance to apoptosis and may explain the well-known association of this enzyme with tumor cell survival and spreading.
The COPI complex functions in nuclear envelope breakdown and is recruited by the nucleoporin Nup153
2003, Developmental Cell
Nuclear envelope breakdown is a critical step in the cell cycle of higher eukaryotes. Although integral membrane proteins associated with the nuclear membrane have been observed to disperse into the endoplasmic reticulum at mitosis, the mechanisms involved in this reorganization remain to be fully elucidated. Here, using Xenopus extracts, we report a role for the COPI coatomer complex in nuclear envelope breakdown, implicating vesiculation as an important step. We have found that a nuclear pore protein, Nup153, plays a critical role in directing COPI to the nuclear membrane at mitosis and that this event provides feedback to other aspects of nuclear disassembly. These results provide insight into how key steps in nuclear division are orchestrated.
Nuclear envelope dynamics in oocytes: From germinal vesicle breakdown to mitosis
2003, Current Opinion in Cell Biology

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Trends in Cell Biology

ForumSorting nuclear membrane proteins at mitosis

Abstract

Section snippets

Mitotic nuclear disassembly and reassembly in somatic cells

Egg extracts: a different world

A nonuniform distribution of nuclear membrane proteins within the mitotic ER?

Acknowledgements

J. Ultrastruct. Res.

Exp. Cell Res.

J. Biol. Chem.

Cell

Curr. Top. Dev. Biol.

Dev. Biol.

Trends Cell Biol.

Trends Cell Biol.

Membrane partitioning during cell division

Annu. Rev. Biochem.

Stepwise reassembly of the nuclear envelope at the end of mitosis

J. Cell Biol.

Integral membrane proteins of the nuclear envelope are dispersed throughout the endoplasmic reticulum during mitosis

J. Cell Biol.

Sequential recruitment of NPC proteins to the nuclear periphery at the end of mitosis

J. Cell Sci.

Nuclear membrane dynamics and reassembly in living cells: targeting of an inner nuclear membrane protein in interphase and mitosis

J. Cell Biol.

Nuclear envelope assembly in Xenopus extracts visualized by scanning EM reveals a transport-dependent ‘envelope smoothing’ event

J. Cell Sci.

Distinct egg membrane vesicles differing in binding and fusion properties contribute to sea urchin male pronuclear envelopes formed in vitro

J. Cell Sci.

Forum
Sorting nuclear membrane proteins at mitosis