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University of Oran 1, Faculty of Medicine, Department of Medicine
Histology-Embryology Department, Dr Hamadouche, Dr Belarbi-Amar
First-Year Medical Cytology Course

THE CYTOSKELETON

I. Definition
The cytoskeleton is a filamentous structure that supports the cell throughout the cytoplasm,
forming a veritable intracellular skeleton.

It performs the following functions:

- The cells maintain their shape, forming a veritable framework.

- Cell mobility: responsible for cell deformation and displacement
- Organelle movement within the cytoplasm.
- Intracellular traffic and molecule transport.
The cytoskeleton is made up of protein filaments, formed by the association of protein
subunits.
These filaments are classified into three categories:
- Actin microfilaments.
- Cell-specific intermediate filaments.
- Microtubules.
These three types are differentiated by their diameter and location within the cell.

II- Elements of the

cytoskeleton: A-

Microtubules
1) Microtubule structure :

Microtubules are tubular cytoskeletal structures made up of globular molecules, the alpha and
beta tubulins. These monomers combine to form a dimer, requiring the hydrolysis of a GPT
molecule thanks to the beta tubulins.

Dimers combine to form polarized protofilaments; 13 protofilaments combine to form a

tubule 25 nm in diameter.

Tubules or microtubules can associate with each other by pooling 3 of their protofilaments

Microtubules have a polarized structure, with a positive pole for polymerization and a
negative pole for depolymerization.

1 Academic year :2019-2020

 University of Oran 1, Faculty of Medicine, Department of Medicine
Histology-Embryology Department, Dr Hamadouche, Dr Belarbi-Amar
First-Year Medical Cytology Course

2) Functions :

-They are considered as rails along which elements will move thanks to ATP molecular
motors; transport of vesicles; macromolecules...

-They play an important role in cell response signalling

-They are part of the centrioles and centrosomes that form the achromatic spindle.

-They form the cell division spindle, and the basic structure of vibratory cilia.

3) Effects of some drugs on microtubules :

• Examples of drugs that block polymerization and depolymerize:
✓ Colchicine
✓ Vinblastine
✓ Nocodazole
• Examples of drugs that block depolymerization:
✓ Taxol
✓ GTPγs (prevents hydrolysis of GTP to GDP)
Some of these drugs are used in the treatment of cancer (taxol). They disrupt cell
dynamics and thus cell replication.
B-Intermediate filaments :
1) Structure :

Intermediate filaments are fibrillar molecules, the most stable component of the cytoskeleton.
Their diameter is between 8 and 10 nm, between that of microtubules and microfilaments.

They are formed by the assembly of filamentous protein monomers; these monomers will
have an N- and C-terminal end; the monomers will assemble to form parallel dimers with
corresponding N- and C-terminal ends.

-Dimers assemble antiparallel into tetramers

The tetramers will join end-to-end, with the C-terminus facing the N-terminus, to form a
protofilament.

-8 protofilaments then assemble to form the 10 nm-thick intermediate filament.

-Intermediate filaments are classified into 4 categories:

2 Academic year :2019-2020

 University of Oran 1, Faculty of Medicine, Department of Medicine
Histology-Embryology Department, Dr Hamadouche, Dr Belarbi-Amar
First-Year Medical Cytology Course

Filament
-
Intermediate FI Protein Location

Epidermi

Type I FI Keratin s Hair

Nails

Vimentine Muscle cell

Type II FI deminer Mesenchymal cell Nerve

Neuroglial fibrillary protein cell

Type III FI Neurofilament Axons and Dendrites

Type IV FI Lamine A B and C Inner face of nuclear envelope

2) Intermediate filament functions:

-Intermediate filaments are stable, resistant structures that play a part in shaping the
cytoskeleton and the cell.

- They are involved in the formation of junctions, which are numerous in

epithelial cells: desmosomes, hemidesmosomes.

- In the cell nucleus, nuclear laminae form a felt-like layer on the inner surface of the
nuclear envelope: the lamina. These laminae are strongly modified during mitosis, allowing
the nuclear envelope to disappear and then to be reconstituted.

C-Microfilaments :
Actin microfilaments, 6 to 7 nm in diameter, are polymers of G-actin globular actin subunits.
In the presence of ATP and calcium, these G-actin monomers combine, using the energy
released by ATP hydrolysis, to form fibrillar F-actin, the tight helical structure at the origin of
microfilaments.

3 Academic year :2019-2020

 University of Oran 1, Faculty of Medicine, Department of Medicine
Histology-Embryology Department, Dr Hamadouche, Dr Belarbi-Amar
First-Year Medical Cytology Course

Like microtubules, microfilaments have a polarized structure: the positive end of

microfilaments elongates faster than the negative end.

It should be noted that microfilaments sometimes associate with other proteins:

⮚ Proteins regulating microfilament polymerization: these are camping proteins that

move around the ends of microfilaments.

⮚ Bundle-maintaining proteins: actin microfilaments can assemble to form bundles,

as in the case of microvilli (where all the microfilaments have the same orientation
and are connected).

⮚ A holding protein, fibrin, bridges the gap between two microfilaments.

⮚ Proteins forming complex structures with microfilaments: for example, in the

muscle cell, F-actin associates with tropomyosin and Troponin to form an actin
microfilament, which plays a role in the attachment of ATPase myosin.

Microfilaments associate with the plasma membrane via binding proteins.

2) Microfilament functions

-In muscle tissue, actin microfilaments are combined with myosin filaments to form the
sarcomere. The sarcomere is the basic myofibril unit of the striated muscle cell, responsible
for muscle contraction.

-Cell-cell junctions (e.g. zonula adhérens) and cell-matrix junctions (focal contacts).

- Have a mechanical role: at microvilli level, they form the non-contractile bundles that
maintain the structure. E.g.: the brush borders of enterocytes.

- Are responsible for cell mobility and deformation: they involve the actin/myosin pair and
are activated during muscle cell contraction or epithelial folding, a frequent phenomenon
during embryogenesis.

-Role in intracellular movement. Actin polymerization drives the movement of endocytosis

vesicles and intracellular organelles.

4) Effects of some drugs on microfilaments :

✓ Cytochalasins: bind to the plus end and block polymerization
✓ Phaloidine: binds to the filament and blocks depolymerization

4 Academic year :2019-2020

University of Oran 1, Faculty of Medicine, Department of Medicine
Histology-Embryology Department, Dr Hamadouche, Dr Belarbi-Amar
First-Year Medical Cytology Course

Microtubules (2)

5 Academic year :2019-2020

University of Oran 1, Faculty of Medicine, Department of Medicine
Histology-Embryology Department, Dr Hamadouche, Dr Belarbi-Amar
First-Year Medical Cytology Course

Centriole and centrosome (2)

Intermediate filaments

6 Academic year :2019-2020

 University of Oran 1, Faculty of Medicine, Department of Medicine
Histology-Embryology Department, Dr Hamadouche, Dr Belarbi-Amar
First-Year Medical Cytology Course

Intermediate filaments (2)

Microfilaments

7 Academic year :2019-2020

 University of Oran 1, Faculty of Medicine, Department of Medicine
Histology-Embryology Department, Dr Hamadouche, Dr Belarbi-Amar
First-Year Medical Cytology Course

III. Pathologies linked to dysfunction of cytoskeletal molecules :

1. Kartagener's syndrome or immobile eyelash syndrome: is
a rare pathology of genetic origin, marked by ciliary dykinesia: (abnormal cilia
beating)
2. Amyotrophic lateral sclerosis: is an autosomal dominant disease caused by a
mutation responsible for a disruption of the cytoskeleton, leading to progressive
muscle paralysis.
References :
1. Cell Biology. Abrégés. Marc Maillet.9th edition, Masson2002.
2. Cell Biology. Abrégés. Marc Maillet.10ème edition, Masson2006
3. Cell Biology. Y Bassaglia. Maloine 2001.
4. Cell Biology. JC Callen. Dunod 2009.
5. Cell Biology .MC Dscamps. PCEM1. Ediscience .2007.
6. Cours de Biologie Cellulaire: Pierre Cau, Raymond Seite. Edition ellipses.1999.
7. Cytology & Cell Physiology. M. Abdelali, H. Benzine-Challam, A.Madoui-
Dekar. Office des Publications Universitaires 2008.
8. The cell and its physiology: M Bendjelloul. Office des Publications Universitaires
2011.
9. Mini manual de Biologie Cellulaire: cours QCM, QROC. J M Petit, S Arico, R Julien.
Dumond 2008.

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