Coordinated events of nuclear assembly

Highlights

• Changes at the chromatin surface initiate nuclear envelope formation and attract membrane from the endoplasmic reticulum.

• Formation of the nascent nuclear envelope depends on membrane remodeling.

• Recent discoveries further inform a mechanism of pore formation as cells exit mitosis.

• Distinct regions of the chromatin disc are associated with different proteins and functions.

Each time a metazoan cell undergoes open mitosis, the nucleus is dismantled in order to partition DNA content to the daughter cells. After chromosomes separate, changes at the chromatin surface usher in reestablishment of nuclear architecture. Proteins destined for the nuclear envelope are attracted to chromatin and concomitantly recruit membrane. As nuclear envelope and protein constituents spread to coat chromatin, distinct regions emerge—some rich in rapid pore formation, others occupied by microtubules that remain attached to kinetochores. Microtubule connections present physical barriers that must be remodeled in order for the nuclear envelope to seal. Regions of the nascent nuclear envelope that are initially characterized by contrasting repertoires of nuclear envelope proteins rapidly coalesce as nuclei expand and enter interphase.

Introduction

The nucleus is a structurally complex organelle that houses and protects the genome, as well as providing an environment that facilitates regulation of genomic information. In addition, intimate association between the nucleus and cytoskeleton expands the role of the nucleus as a central organizing hub of the cell [1]. Several human diseases are characterized by defects in nuclear architecture, underscoring a link between proper nuclear organization and normal cell function ([2] and see Dorado and Andrés, this issue). A foundational component of nuclear architecture is the nuclear envelope (NE), a double membrane barrier that separates the nucleoplasm from the cytoplasm. The outer nuclear membrane (ONM) is contiguous with both the inner nuclear membrane (INM) and the endoplasmic reticulum (ER). The former connectivity occurs at sites where nuclear pore complexes (NPCs) create channels in the nuclear envelope, each surrounded by a highly curved region of membrane connecting INM to ONM. NPCs are large proteinaceous structures that provide sites of selective macromolecular transport across the NE. Embedded within both outer and inner nuclear membranes are transmembrane proteins that form a network of interactions, spanning from the cytoskeleton to the NE lumen to the meshwork of lamin proteins that lines the INM termed the nuclear lamina. Interconnectivity between these elements of nuclear architecture is reinforced by interactions between lamin proteins and both nuclear pore complex components and INM proteins (e.g., [3]). Further, the INM protein SUN1 localizes in proximity to NPCs, suggesting the presence of an NPC influences the neighboring membrane protein repertoire [4].

When cells undergo an open mitosis, the highly integrated architecture of the nucleus is dismantled before partitioning the genome. Once sister chromatids separate in anaphase, nuclear envelope proteins target to the chromatin surface, mediating rapid engulfment of chromosomes by membrane. ONM and INM proteins, constituents of NPCs, and lamins rely on distinct mechanisms of recruitment and transiently enrich at discrete regions of the chromatin surface as the nucleus forms. These targeting events are coordinated within an astonishingly rapid timeframe—a notable and important feat considering that disrupted nuclear architecture can result in significant deleterious consequences for the cell [2]. Here, we will focus on how nuclear assembly, and establishment of the nuclear envelope composition that underpins nuclear architecture, is accomplished with each cell division.