Nuclear Membrane: What is it? Structure, Function and Associated Diseases

It is found only in eukaryotic cells, because only eukaryotic cells have nuclei.

The nuclear membrane protects and covers the chromatin and the nucleus. It works very similar to the cell membrane in that it performs basically the same functions as the cell membrane, with the exception that it is applying the functions to the nucleus of the cell.

The nuclear membrane has nuclear pores, which are selectively permeable as they restrict what enters and leaves the nucleus.

Structure of the nuclear membrane

The nuclear envelope has two membranes, each with the typical membrane structure of the cell. Each membrane is made up of a double bilayer. This means that it has four total layers of phospholipids that form two distinct bilayers.

The outermost membrane is attached to the rough endoplasmic reticulum and has ribosomes attached to it. The inner nuclear membrane has chromatin attached to it.

The nuclear membrane is entangled in a network of filaments that give it stability.

The nuclear lamina consists of “intermediate filaments”, 30 to 100 nm thick. These intermediate filaments are polymers .

Within the two membranes a space filled with filamentous material is observed.

In the space between the two outer and inner membranes, they fuse in some areas, creating protein channels called nuclear pores, which favor the selective transport of substances between the nucleus and the cell cytoplasm.

Nuclear pores form at sites where the inner and outer membranes of the nuclear envelope meet. These have a diameter between 50 to 100 nm.

They have a complex structure, made up of proteins that form a ring and internally coat the pore structure, called nucleoporins.

Sometimes a thin diaphragm can be seen running horizontally through the pore. Furthermore, the chromatin that carries the genetic material is organized in such a way as to create a space or pathway for the nuclear pore.

The outer bilayer interacts with the cytoplasm and is physically connected to the rough endoplasmic reticulum. Actually, the rough endoplasmic reticulum can be thought of as an extension of the outer nuclear bilayer.

This close membrane connectivity allows messenger ribonucleic acid to pass directly from deoxyribonucleic acid in the nucleus to ribosomes in the rough endoplasmic reticulum, without coming into contact with the relatively harsh environment of the cytoplasm.

The negative staining technique is one of the most widely used techniques to study nuclear pores. This procedure deposits heavy metals around the structures and the surface structure is delineated.

When placed in an electron microscope, the heavy metal around the structure retards the electron beam.

A “negative” image is created in the photograph, of the pore structure, since the structures allow the passage of the electron beam, activating the photographic emulsion.

Another way to visualize nuclear pores is by freezing. This process involves the rapid freezing of structures followed by fracturing.

The membranes are separated along the lipid bilayer and the side near the cytoplasm or the extracellular side of the membrane is shown.

The membrane is then replicated by evaporating the heavy metal on the surface. This replica is what you see in the transmission electron microscope.

Nuclear membrane function

Transport of material through the nuclear pore

The pore behaves like a channel full of fluids by means of which the transport is carried out, which is very frequent and fast, and is carried out in both directions indistinctly and even simultaneously.

This transport can occur in several ways:

By diffusion

Simple diffusion is the type of transport carried out by substances with a size smaller than 50 kDa.

Passive transport facilitated

Like diffusion transport, these transports are carried out against the gradient and it is the type of transport of the largest substances.

Active transport

This form of transport is assumed when molecules larger than the pore diameter enter the nucleus. This transport requires energy expenditure (ATP).

The pore can actually expand to 26 nm when it receives the proper signal. Studies have shown that the signal is in the peptide sequences.

These are recognition sequences rich in lysine, arginine, and proline. The signal can control the direction of RNA transport.

Cell reproduction

The inner nuclear bilayer is packed with proteins that interact with the contents of the nucleus, especially DNA.

Filaments called laminates connect chromosomes to proteins in the inner membrane and help the nucleus maintain its shape. The space between the two bilayers is called the perinuclear space.

Transcription factors, mRNA, and some other small individuals move through the bilayers and the perinuclear space through large channels called nuclear pores.

The most fascinating aspect of these pores is that they can expand and contract to allow or block the access of larger molecules through the nuclear membrane, similar to how the pupil of your eye enlarges or narrows to allow more or less less light reaches the retina.

Finally, as the cell prepares for reproduction, proteins in the cytoplasm dissolve the nuclear membrane so that duplicated DNA can separate on opposite sides of the cell.

They can play a role in assembly and disassembly before and after mitosis.

After they are phosphorylated, this triggers the dismantling of the lamina and causes the nuclear envelope to dissolve into vesicles.

Dephosphorylation reverses this and allows the nucleus to reform.

After cell division, new nuclear membranes form in the two “daughter” cells and their vital functions resume to protect DNA and provide communication between the nucleus and the rest of the cell.

The nuclear lamina is also involved in the organization of chromatin.

Nuclear membrane associated diseases

In the last decade, a wide range of fascinating monogenic diseases have been linked to mutations in the gene encoding type A nuclear laminae.

Among the clinical diseases that predominantly affect the skeletal muscle, adipose and peripheral nerve, or give a phenotype of Progeria, we have:

Striated muscle

  • Autosomal dominant (and rarely recessive) Emery-Dreifuss muscular dystrophy.
  • Dilated cardiomyopathy 1A.
  • Type 1B girdle muscular dystrophy.
  • Congenital muscular dystrophy.
  • “Heart-hand” syndrome.

Adipose tissue

  • Dunnigan-type familial partial lipodystrophy.
  • Lipoatrophy with diabetes and other features of insulin resistance.
  • Atypical lipodystrophy syndromes.
  • Mandibuloacral dysplasia.

Peripheral nerve

  • Charcot-Marie-Tooth disease type 2B1.

Progeria phenotype

  • Hutchinson-Gilford progeria syndrome.
  • Atypical Werner syndrome.
  • Assorted progeroid disorders.
  • Mandibuloacral dysplasia.

Several diseases are also caused by mutations in genes encoding type B lamellae and proteins that associate with the nuclear lamina.

Studies of these so-called laminopathies or nuclear envelopes, some of which are common human disorders of phenocopy, provide clues about the functions of the nuclear envelope and insights into the pathogenesis of disease and human aging.

Diseases caused by mutations in genes encoding laminae or type B proteins associated with the nuclear lamina:

  • Cardiomyopathy with muscular dystrophy.
  • Pelger-Huët anomaly (heterocigota).
  • Skeletal Greenberg dysplasia (homocygotic).
  • Sclerosing bone dysplasias.
  • Ataxia cerebelosa.
  • Distonía.
  • Autosomal dominant leukodystrophy of adults.
  • Acquired partial lipodystrophy.
  • Restrictive dermopathy and progeroid disorders.