The nucleus plays a role in supporting the cell, but it is also the seat of our genetic program. This is because it contains our DNA in the form of a complex called chromatin. Explanations.

The nucleus is located at the center or at the periphery of the cell depending on the function of the latter. It is present in eukaryotic cellular organisms.

As a reminder, the term eukaryote designates all of the unicellular or multicellular organisms whose cells generally have a nucleus and organelles delimited by membranes. However, in some eukaryotes there are cells lacking a nucleus. In humans, this is particularly the case with red blood cells. The eukaryote is opposed to the prokaryote which characterizes a microorganism whose cell lacks a nucleus and a delimited organelle.

The nucleus varies in shape depending on the cell type (for example, it is spherical in neurons and ovoid in fibroblasts). Its diameter is a few micrometers (5 to 6 µm) and it generally represents less than 10% of the total cell volume.

The kernel is bathed in the cytoplasm, aqueous gel found in the cell. The nucleus is separated from the cytoplasm by a nuclear envelope. This consists of two spaced membranes which merge in certain places forming openings or “nuclear pores”. These allow the passage of molecules between the nucleus and granular endoplasmic reticulum surrounding the latter. The inner membrane merges with the nucleus while the outer membrane is an integral part of the rough endoplasmic reticulum. This last organelle is the place of synthesis of proteins secreted outside the cell and of proteins and lipids which constitute the membranes of other cellular organelles (Golgi apparatus, lysosome, nucleus, ribosomes, vesicles, mitochondria, etc.).

The cell nucleus is made up of chromatin but also of the nucleolus, the nucleoplasm and finally a nuclear membrane which separates it from the rest of the cell. This membrane is dotted with ribosomes and has pores that allow molecular exchanges between the cell and the nucleus.

Chromatin is a structure in which DNA is packaged and compacted in the limited volume of the nucleus. Chromatin is made up of discontinuous subunits called chromosomes. It is usually diffuse but condenses during cell division (mitosis). Chromatin is bathed in a watery liquid called the nucleoplasm.

There are two types of chromatin: euchromatin which is mainly found in the center of the nucleus, it is not very compact and has genes that are expressed. Then heterochromatin located largely on the periphery of the nucleus, it is compact and its genes are little or not expressed.

The nuclear envelope surrounds the nucleus. It consists of two membranes separated by a space:

• the inner membrane merges with the nucleus itself. It is covered by a network of proteins called the nuclear lamina and it has calcium channels that allow the release of calcium ions into the nucleus. The lamina is a dense fibrillar mesh made up of lamins and membrane proteins. It ensures the shape and solidity of the core;
• the outer membrane forms a continuity with the granular endoplasmic reticulum (which surrounds the nucleus) and may be (like the latter) studded with ribosomes on its cytoplasmic surface. The outer membrane maintains the cytoskeleton of the cell thanks to the proteins that constitute it;
• nuclear pores allow molecular exchanges between the interior of the nucleus and the rest of the cell (cytoplasm). These exchanges include the exit of messenger RNAs from the nucleus to the cytoplasm and the entry of nucleotides into the nucleus and necessary for the synthesis of RNAs.
• the nucleolus is a very active place of transcription of DNA into RNA. The RNAs produced byThe nucleolus are then exported to the cytoplasm to be used in the machinery which makes it possible to transcribe the RNA into proteins.

A supporting role

The nucleus is a delimited organelle which participates in the organization of the eukaryotic cell.

The nucleus serves as a support for the nuclear envelope. In fact, the lamins (proteins organized in a perpendicular mesh) form a structure which supports the nuclear membrane at the periphery of the nucleus. The nuclear membrane separates the cell from the nucleus, the cradle of our genome.

The nucleus, seat of the genetic program

The nucleus is the place of DNA synthesis (carried out during the replication for cell division) andRNA (for the transcription). The nucleus also holds the nucleolus, place of transcription of ribosomal RNAs.

There is a strong link between nuclear envelope abnormalities and many genetic diseases. These pathologies compromise the entire organism:

• muscle tissue;
• heart tissue;
• nerve tissue.

The best-known example of these conditions is that of progeria, a serious disease whose main symptom is accelerated aging which considerably reduces the patient’s life expectancy.

These diseases are gathered within the same family: laminopathies. The latter constitute a very heterogeneous set of genetic diseases characterized by mutations in the LMNA gene encoding nuclear proteins called lamins. The lamines form a layer, the lamina, which lines the inner surface of the nucleus, and gives it its shape. Associated with other proteins, the lamins constitute the nucleoskeleton which occupies the entire nuclear volume. Lamins not only have a role in nuclear architecture, but they also participate in DNA transcription, duplication and repair.

Here is the list of the different laminopathies referenced to date:

• diseases with preferential neuromuscular expression (manifested by early retractions, muscle weakness and cardiac damage): Emery Dreifuss muscular dystrophy type II (AD-EMD), girdle muscular dystrophy type 1B (LGMD1B) , LMNA-related congenital muscular dystrophy (L-CMD), etc. ;
• Diseases with isolated cardiac expression: dilated cardiomyopathy with conduction disturbances, non-compaction of the left ventricle (LVNC), arrhythmogenic cardiomyopathy of the right ventricle (CAVD);
• neurological diseases: form of autosomal recessive axonal neuropathy of Charcot-Marie-Tooth (CMT type 2B1);
• metabolic diseases: familial partial Dunnigan lipodystrophy (FPLD);
• diseases linked to abnormalities in aging: Hutchinson-Gilford syndrome or progeria (HGPS), acro-mandibular dysplasia (MAD).

The diagnosis of laminopathies (pathologies linked to mutations in the LMNA gene encoding the lamins, proteins lining the inner surface of the nucleus) is based on:

• a clinical examination which reveals symptoms of a muscular and / or cardiac nature;
• additional examinations which make it possible to specify the diagnosis: blood samples, muscle exams (electromyogram, imaging, etc.), examinations of cardiac function (electrocardiogram, echocardiography, etc.), imaging of other organs;
• molecular analyzes that make it possible to confirm the diagnosis on the genetic level. In the case of laminopathies, the genetic diagnosis consists of the direct analysis of the LMNA gene.

Laminopathies (pathologies linked to mutations in the LMNA gene encoding the lamins, proteins lining the inner surface of the nucleus) are incurable diseases, the treatment is palliative and multidisciplinary:

• regular orthopedic care, in particular through physiotherapy;
• respiratory care based on respiratory physiotherapy and assisted mechanical ventilation;
• regular cardiological monitoring is essential: taking medication, placing a pacemaker or a defibrillator and sometimes even heart transplantation are essential to ensure the patient’s survival;
• the Neuromuscular Disease Care and Emergency Card promotes the coordination of care for neuromuscular diseases and reduces the risk of medical error for these unrecognized diseases. It is very useful in an emergency. It is recommended to always have it with you;
• genetic counseling helps inform and support a person, or a family, faced with the risk of developing or transmitting a genetic disease.