Remodeling the nuclear membrane during closed mitosis

The mitotic spindle assembly and chromosome segregation in eukaryotes must be coordinated with the nuclear envelope (NE) remodeling. In a so-called ‘open’ mitosis the envelope of the mother nucleus is dismantled allowing the cytoplasmic spindle microtubules to capture the chromosomes. Alternatively, cells undergoing ‘closed’ mitosis assemble the intranuclear spindle and divide the nucleus without ever losing the nucleocytoplasmic compartmentalization. Here we focus on the mechanisms underlying mitotic NE dynamics in unicellular eukaryotes undergoing a closed nuclear division, paying specific attention to the emerging roles of the lipid biosynthesis machinery in this process. We argue that lessons learned in these organisms may be generally relevant to understanding the NE remodeling and the evolution of mitotic mechanisms throughout the eukaryotic domain.

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.