Remodeling the nuclear membrane during closed mitosis
Introduction
Invention of the nucleus segregated from the cytoplasm by a selectively permeable membrane barrier has been a fundamental step in the advent of eukaryotic life. This called for integration of the nuclear membrane dynamics within the cellular physiology framework and in particular, its coordination with inheritance of the genetic material. Eukaryotes segregate duplicated chromosomes during mitosis using the microtubule-based spindle apparatus. This poses a spatial quandary since microtubules are normally located in the cytoplasm, where they function in intracellular transport and polarity establishment. Thus, either the nuclear membrane must break down early in mitosis to allow microtubules to capture the chromosomes or cells have to assemble an intranuclear mitotic spindle by importing the microtubule subunits and microtubule-associated proteins into an intact nucleus. The modern eukaryotes use both strategies – known as the open and the closed mitosis – and a host of variations in between. This raises the questions of specific functional adaptations required for different types of mitoses, possible physiological advantages of distinct division modes and the degree of plasticity in this integral cell biological mechanism.
The nuclear envelope (NE) is an elaboration of the endomembrane system that consists of two lipid bilayers called the outer (ONM) and the inner nuclear membrane (INM). The ONM is continuous with the endoplasmic reticulum (ER), suggesting a close relationship between the NE and the general ER dynamics. The INM is occupied by a network of proteins interacting with the chromatin and contributing to the nuclear structure and function. The two NE membranes are fused at the nuclear pores, the sites of nucleocytoplasmic exchange decorated with multisubunit nuclear pore complexes (NPCs) [1]. Unlike the complex NE dynamics during open mitosis that involves NPC and nuclear lamina disassembly, release of the nuclear proteins and dispersal of the NE membranes into the ER, followed by their reassembly into the daughter nuclei [1, 2], the closed nuclear division is essentially, a study in membrane remodeling. The major steps of this process include insertion of the microtubule-organizing centers (MTOCs) into the NE, anaphase nuclear membrane expansion and the fission of the nuclear membrane to yield two independent daughter nuclei. In this review, we will discuss mostly the membrane events preceding daughter nuclei individuation.
Section snippets
Membrane remodeling at the spindle pole body-nuclear envelope insertion sites
The spindle pole bodies (SPBs) serve as the MTOCs for the mitotic spindle in many lower eukaryotes. The SPB is a morphologically stratified structure duplicating once in each cell cycle [3, 4]. Its inner plaque faces the nuclear interior and nucleates and anchors the spindle microtubules, whereas the outer plaque projects into the cytoplasm and nucleates the astral microtubule arrays. The central core ensures structural integrity of the SPB and anchors it within the NE plane. In budding yeast,
Cell cycle control of the SPB–NE insertion in fission yeast
The failure to integrate the SPBs in the S. pombe Brr6 mutants appears to parallel the consequences of mutating the Ndc1 ortholog Cut11 [27] and the mitotic regulator Cut12 [16, 28]. While the effect of Cut11 deficiency is probably owing to a physical failure in anchoring the SPB within a fenestra, similar to its function in the NPC insertion, the reasons for the Cut12-related phenotype are less clear. Cut12 is an essential protein that lacks the membrane association domains; instead, it
Scaling considerations in closed nuclear division
To accommodate spindle elongation and a closed division of the spherical mother nucleus into two daughters, the nuclear surface area increases during anaphase and it does so in a non-scalable manner [34]. For instance, a dividing S. pombe nucleus increases its surface area by approximately 30% by the end of mitosis while the nuclear volume remains constant [34, 35••]. This is not a simple issue of passively drawing the membrane material from the peripheral ER by the elongating nucleus. Arguing
Striking diversity of mitotic mechanisms
The importance of assembling a membrane reservoir to enable the closed nuclear division is underscored by the unusual mitotic strategy of the fission yeast Schizosaccharomyces japonicus (S. japonicus) [35••, 55•]. S. japonicus builds the intranuclear spindle and initiates the closed type of mitosis in a manner similar to its relative S. pombe. However, the S. japonicus nucleus fails to divide through the typical dumbbell intermediate. Instead, it elongates into diamond-like and bow-like shapes
References and recommended reading
Papers of particular interest, published within the period of review, have been highlighted as:
• of special interest
•• of outstanding interest
Acknowledgements
We are grateful to E. Makeyev and A. Vjestica for discussions and suggestions on the manuscript. Our work is supported by Singapore Millenium Foundation.
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A model for bridging microtubule dynamics with nuclear envelope shape evolution during closed mitosis
2020, Journal of the Mechanics and Physics of SolidsCitation Excerpt :In contrast, confining chromosomes within the intact NE during division are observed in many unicellular eukaryotes like fission yeast Schizosaccharomyces pombe (S. pombe) (Smoyer and Jaspersen, 2014), a process referred to as closed mitosis. It has been recognized that partially overlapped anti-parallel spindle microtubules (Ding et al., 1997), nucleated from two spindle pole bodies (SPBs) at two poles of the NE (Zhang and Oliferenko, 2013), are responsible for generating propelling forces to drive closed mitosis. Specifically, studies have shown that motor protein kinesins can create the poleward force to slide overlapped microtubules and drive the deformation of NE: from a sphere to a spherical cylinder, then a peanut/dumbbell and eventually a barbell.
Cell Biology: An Open Solution for Closed Mitosis
2020, Current BiologyCompartmentalized Synthesis of Triacylglycerol at the Inner Nuclear Membrane Regulates Nuclear Organization
2019, Developmental CellCitation Excerpt :The internal membrane systems of the eukaryotic cell are highly dynamic, and their regulated remodeling is essential for proper organelle function, during both normal cell growth and stress. For example, the nuclear membrane undergoes dynamic remodelling during the two modes of nuclear division operating in eukaryotes, “open” and “closed” mitosis (Zhang and Oliferenko, 2013; Ungricht and Kutay, 2017), and the accumulation of unfolded proteins in the endoplasmic reticulum (ER) drives significant ER membrane expansion in order to support increased protein folding capacity (Walter and Ron, 2011). Therefore, cells must possess mechanisms to selectively add, remove, or remodel membrane phospholipids at different organelles in response to cell cycle and stress signals, but those remain poorly understood.
The lamin code
2018, BioSystemsChromosomes Orchestrate Their Own Liberation: Nuclear Envelope Disassembly
2017, Trends in Cell BiologyCitation Excerpt :Fenestration is tightly coordinated with the mitotic entry/exit program via mechanisms that are only beginning to be defined. For instance, activity of the central cell cycle regulatory kinase (Cdc2, the fission yeast CDK) is locally controlled by Cut12, an SPB protein that integrates CDK input with that of other cell cycle regulatory kinases (e.g., the Polo and Never In Mitosis or NIMA kinases) that impinge upon mitotic entry [64,65]. The loss of Cut12 leads to a failure of the SPB to commence insertion [66,67], even though localized NEBD occurs; hence, Cut12 is required for the coupling between NE fenestration and SPB insertion.