The nuclear envelope, also known as the nuclear membrane, is made up of two

lipid bilayer The lipid bilayer (or phospholipid bilayer) is a thin polar membrane made of two layers of lipid molecules. These membranes form a continuous barrier around all cell (biology), cells. The cell membranes of almost all organisms and many viruses a ...

membrane A membrane is a selective barrier; it allows some things to pass through but stops others. Such things may be molecules, ions, or other small particles. Membranes can be generally classified into synthetic membranes and biological membranes. Bi ...

s that in eukaryotic cells surround the nucleus, which encloses the

genetic material Nucleic acids are large biomolecules that are crucial in all cells and viruses. They are composed of nucleotides, which are the monomer components: a 5-carbon sugar, a phosphate group and a nitrogenous base. The two main classes of nucleic aci ...

. The nuclear envelope consists of two lipid bilayer membranes: an inner nuclear membrane and an outer nuclear membrane. The space between the membranes is called the perinuclear space. It is usually about 10–50 nm wide. The outer nuclear membrane is continuous with the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

membrane. The nuclear envelope has many

nuclear pore The nuclear pore complex (NPC), is a large protein complex giving rise to the nuclear pore. A great number of nuclear pores are studded throughout the nuclear envelope that surrounds the eukaryote cell nucleus. The pores enable the nuclear tran ...

s that allow materials to move between the

cytosol The cytosol, also known as cytoplasmic matrix or groundplasm, is one of the liquids found inside cells ( intracellular fluid (ICF)). It is separated into compartments by membranes. For example, the mitochondrial matrix separates the mitochondri ...

and the nucleus. Intermediate filament proteins called

lamin Lamins, also known as nuclear lamins, are fibrous proteins in Intermediate filament#Type V – nuclear lamins, type V intermediate filaments, providing structural function and Transcription (biology), transcriptional regulation in the cell nucle ...

s form a structure called the

nuclear lamina The nuclear lamina is a dense (~30 to 100 nm thick) fibrillar network inside the nucleus of eukaryote cells. It is composed of intermediate filaments and membrane associated proteins. Besides providing mechanical support, the nuclear lam ...

on the inner aspect of the inner nuclear membrane and give structural support to the nucleus.

Structure

The nuclear envelope is made up of two lipid bilayer membranes, an inner nuclear membrane and an outer nuclear membrane. These membranes are connected to each other by nuclear pores. Two sets of intermediate filaments provide support for the nuclear envelope. An internal network forms the

on the inner nuclear membrane. A looser network forms outside to give external support. The actual shape of the nuclear envelope is irregular. It has invaginations and protrusions and can be observed with an

electron microscope An electron microscope is a microscope that uses a beam of electrons as a source of illumination. It uses electron optics that are analogous to the glass lenses of an optical light microscope to control the electron beam, for instance focusing it ...

Nuclear envelope of one cancerous HeLa cell

Outer membrane

The outer nuclear membrane also shares a common border with the

. While it is physically linked, the outer nuclear membrane contains proteins found in far higher concentrations than the endoplasmic reticulum. All four

nesprin Nesprins (nuclear envelope spectrin repeat proteins) are a family of proteins that are found primarily in the outer nuclear membrane, as well as other subcellular compartments. They contain a C-terminal KASH transmembrane domain and are part of ...

proteins (nuclear envelope spectrin repeat proteins) present in mammals are expressed in the outer nuclear membrane. Nesprin proteins connect cytoskeletal filaments to the nucleoskeleton. Nesprin-mediated connections to the cytoskeleton contribute to nuclear positioning and to the cell’s mechanosensory function. KASH domain proteins of Nesprin-1 and -2 are part of a

LINC complex The linker of nucleoskeleton and cytoskeleton (LINC) complex is a protein complex associated with both inner and outer membranes of the nucleus. It is composed of SUN-domain proteins and KASH-domain proteins. The SUN-domain proteins are membrane- ...

(linker of nucleoskeleton and cytoskeleton) and can bind directly to cystoskeletal components, such as

actin filaments Microfilaments, also called actin filaments, are protein filaments in the cytoplasm of eukaryotic cells that form part of the cytoskeleton. They are primarily composed of polymers of actin, but are modified by and interact with numerous other p ...

, or can bind to proteins in the perinuclear space. Nesprin-3 and -4 may play a role in unloading enormous cargo; Nesprin-3 proteins bind

plectin Plectin is a giant protein found in nearly all mammalian cells which acts as a link between the three main components of the cytoskeleton: actin microfilaments, microtubules and intermediate filaments. In addition, plectin links the cytoskeleto ...

and link the nuclear envelope to cytoplasmic intermediate filaments. Nesprin-4 proteins bind the plus end directed motor kinesin-1. The outer nuclear membrane is also involved in development, as it fuses with the inner nuclear membrane to form nuclear pores.

Inner membrane

The inner nuclear membrane encloses the

nucleoplasm The nucleoplasm, also known as karyoplasm, is the type of protoplasm that makes up the cell nucleus, the most prominent organelle of the eukaryotic cell. It is enclosed by the nuclear envelope, also known as the nuclear membrane. The nucleoplasm r ...

, and is covered by the

, a mesh of

intermediate filaments Intermediate filaments (IFs) are cytoskeletal structural components found in the cells of vertebrates, and many invertebrates. Homologues of the IF protein have been noted in an invertebrate, the cephalochordate ''Branchiostoma''. Intermedi ...

which stabilizes the nuclear membrane as well as being involved in chromatin function. It is connected to the outer membrane by

nuclear pores The nuclear pore complex (NPC), is a large protein complex giving rise to the nuclear pore. A great number of nuclear pores are studded throughout the nuclear envelope that surrounds the eukaryote cell nucleus. The pores enable the nuclear tran ...

which penetrate the membranes. While the two membranes and the endoplasmic reticulum are linked, proteins embedded in the membranes tend to stay put rather than dispersing across the continuum. It is lined with a fiber network called the nuclear lamina which is 10-40 nm thick and provides strength. Mutations in the

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

s that encode for the

inner nuclear membrane proteins Inner nuclear membrane proteins (INM proteins) are membrane proteins that are embedded in or associated with the inner membrane of the nuclear envelope. There are about 60 INM proteins, most of which are poorly characterized with respect to str ...

can cause several

laminopathies Laminopathies ('' lamino-'' + '' -pathy'') are a group of rare genetic disorders caused by mutations in genes encoding proteins of the nuclear lamina. Since the first reports of laminopathies in the late 1990s, increased research efforts have sta ...

Nuclear pores

The nuclear envelope is punctured by around a thousand

nuclear pore complexes The nuclear pore complex (NPC), is a large protein complex giving rise to the nuclear pore. A great number of nuclear pores are studded throughout the nuclear envelope that surrounds the eukaryote cell nucleus. The pores enable the nuclear tran ...

, about 100 nm across, with an inner channel about 40 nm wide. The complexes contain a number of

nucleoporin Nucleoporins are a family of proteins which are the constituent building blocks of the nuclear pore complex (NPC). The nuclear pore complex is a massive structure embedded in the nuclear envelope at sites where the inner and outer nuclear memb ...

s, proteins that link the inner and outer nuclear membranes.

Cell division

During the G2 phase of

interphase Interphase is the active portion of the cell cycle that includes the G1, S, and G2 phases, where the cell grows, replicates its DNA, and prepares for mitosis, respectively. Interphase was formerly called the "resting phase," but the cell i ...

, the nuclear membrane increases its surface area and doubles its number of nuclear pore complexes. In

eukaryotes The eukaryotes ( ) constitute the domain of Eukaryota or Eukarya, organisms whose cells have a membrane-bound nucleus. All animals, plants, fungi, seaweeds, and many unicellular organisms are eukaryotes. They constitute a major group of ...

such as

yeast Yeasts are eukaryotic, single-celled microorganisms classified as members of the fungus kingdom (biology), kingdom. The first yeast originated hundreds of millions of years ago, and at least 1,500 species are currently recognized. They are est ...

which undergo closed

mitosis Mitosis () is a part of the cell cycle in eukaryote, eukaryotic cells in which replicated chromosomes are separated into two new Cell nucleus, nuclei. Cell division by mitosis is an equational division which gives rise to genetically identic ...

, the nuclear membrane stays intact during cell division. The spindle fibers either form within the membrane, or penetrate it without tearing it apart. In other eukaryotes (animals as well as plants), the nuclear membrane must break down during the

prometaphase Prometaphase is the phase of mitosis following prophase and preceding metaphase in eukaryotic somatic cells. In prometaphase, the nuclear membrane breaks apart into numerous "membrane vesicles," and the chromosomes inside form protein structure ...

stage of mitosis to allow the mitotic spindle fibers to access the chromosomes inside. The breakdown and reformation processes are not well understood.

Breakdown

In mammals, the nuclear membrane can break down within minutes, following a set of steps during the early stages of

. First, M-Cdk's phosphorylate

polypeptides Peptides are short chains of amino acids linked by peptide bonds. A polypeptide is a longer, continuous, unbranched peptide chain. Polypeptides that have a molecular mass of 10,000 Da or more are called proteins. Chains of fewer than twenty ami ...

and they are selectively removed from the nuclear pore complexes. After that, the rest of the nuclear pore complexes break apart simultaneously. Biochemical evidence suggests that the nuclear pore complexes disassemble into stable pieces rather than disintegrating into small polypeptide fragments. M-Cdk's also phosphorylate elements of the nuclear lamina (the framework that supports the envelope) leading to the disassembly of the lamina and hence the envelope membranes into small vesicles.

Electron The electron (, or in nuclear reactions) is a subatomic particle with a negative one elementary charge, elementary electric charge. It is a fundamental particle that comprises the ordinary matter that makes up the universe, along with up qua ...

and

fluorescence microscopy A fluorescence microscope is an optical microscope that uses fluorescence instead of, or in addition to, scattering, reflection, and attenuation or absorption, to study the properties of organic or inorganic substances. A fluorescence micro ...

has given strong evidence that the nuclear membrane is absorbed by the endoplasmic reticulum—nuclear proteins not normally found in the endoplasmic reticulum show up during mitosis. In addition to the breakdown of the nuclear membrane during the prometaphase stage of

, the nuclear membrane also ruptures in migrating mammalian cells during the

stage of the cell cycle. This transient rupture is likely caused by nuclear deformation. The rupture is rapidly repaired by a process dependent on "endosomal sorting complexes required for transport" ( ESCRT) made up of

ic protein complexes. During nuclear membrane rupture events, DNA double-strand breaks occur. Thus the survival of cells migrating through confined environments appears to depend on efficient nuclear envelope and

DNA repair DNA repair is a collection of processes by which a cell (biology), cell identifies and corrects damage to the DNA molecules that encode its genome. A weakened capacity for DNA repair is a risk factor for the development of cancer. DNA is cons ...

machineries. Aberrant nuclear envelope breakdown has also been observed in laminopathies and in cancer cells leading to mislocalization of cellular proteins, the formation of micronuclei and genomic instability.

Reformation

Exactly how the nuclear membrane reforms during

telophase Telophase () is the final stage in both meiosis and mitosis in a eukaryotic cell. During telophase, the effects of prophase and prometaphase (the nucleolus and nuclear membrane disintegrating) are reversed. As chromosomes reach the cell poles, ...

of mitosis is debated. Two theories exist— * Vesicle fusion — where vesicles of nuclear membrane fuse together to rebuild the nuclear membrane * Re-shaping of the endoplasmic reticulum—where the parts of the endoplasmic reticulum containing the absorbed nuclear membrane envelop the nuclear space, reforming a closed membrane.

Origin of the nuclear membrane

A study of the comparative

genomics Genomics is an interdisciplinary field of molecular biology focusing on the structure, function, evolution, mapping, and editing of genomes. A genome is an organism's complete set of DNA, including all of its genes as well as its hierarchical, ...

evolution Evolution is the change in the heritable Phenotypic trait, characteristics of biological populations over successive generations. It occurs when evolutionary processes such as natural selection and genetic drift act on genetic variation, re ...

and origins of the nuclear membrane led to the proposal that the nucleus emerged in the primitive

eukaryotic The eukaryotes ( ) constitute the Domain (biology), domain of Eukaryota or Eukarya, organisms whose Cell (biology), cells have a membrane-bound cell nucleus, nucleus. All animals, plants, Fungus, fungi, seaweeds, and many unicellular organisms ...

ancestor (the “prekaryote”), and was triggered by the archaeo-bacterial symbiosis. Several ideas have been proposed for the evolutionary origin of the nuclear membrane. These ideas include the invagination of the plasma membrane in a prokaryote ancestor, or the formation of a genuine new membrane system following the establishment of proto-

mitochondria A mitochondrion () is an organelle found in the cells of most eukaryotes, such as animals, plants and fungi. Mitochondria have a double membrane structure and use aerobic respiration to generate adenosine triphosphate (ATP), which is us ...

in the archaeal host. The adaptive function of the nuclear membrane may have been to serve as a barrier to protect the genome from

reactive oxygen species In chemistry and biology, reactive oxygen species (ROS) are highly Reactivity (chemistry), reactive chemicals formed from diatomic oxygen (), water, and hydrogen peroxide. Some prominent ROS are hydroperoxide (H2O2), superoxide (O2−), hydroxyl ...

(ROS) produced by the cells' pre-mitochondria.Bernstein H, Bernstein C. Sexual communication in archaea, the precursor to meiosis. pp. 103-117 in Biocommunication of Archaea (Guenther Witzany, ed.) 2017. Springer International Publishing DOI 10.1007/978-3-319-65536-9

Notes

References

External links

*
Animations of nuclear pores and transport through the nuclear envelope

Illustrations of nuclear pores and transport through the nuclear membrane
* {{Authority control Membrane biology Nuclear substructures