Cytoskeleton / fixed orthodontics courses

CYTOSKELETON
INDIAN DENTAL ACADEMY
Leader in continuing Dental Education
www.indiandentalacademy.com

REFERENCES :
• Tencate’s oral histology, development, structure and
function. Sixth edition.
• Medical Physiology- William F. Ganong
• Textbook of histology, Hams.
• Textbook of oral anatomy, histology and embryology.
Third edition. B.K Berkovitz.
• Basic Pathology, Robbins.www.indiandentalacademy.com

LEARNING OBJECTIVES
At the end of the seminar, one should be able to
understand the :
• Structural elements of cytoskeleton
• Functions of each structure
• Clinical considerations

CONTENTS
• Overview of cell structure
• History and introduction of cytoskeleton
• Structural elements of cytoskeleton
• Clinical considerations
• Cytoskeleton based structures
• Conclusion

OVERVIEW OF CELL STRUCTURE
• Within cells there is an intricate network of organelles
and proteins that all have unique functions. These
organelles allow the cell to function properly.

CYTOSKELETON

HISTORY
• In 1903, Nikolai K Koltsov proposed that the shape
of cells was determined by a network of tubules
which he termed the cytoskeleton.
• The term Cytosquelette (in French) was first
introduced by French embryologist Paul Wintrebert
in 1931.

INTRODUCTION
• The cytoskeleton is a cellular "scaffolding” or
"skeleton" contained within a cell's cytoplasm and is
made out of protein.
• The cytoskeleton is present in all cells.
• It was once thought to be unique to eukaryotes, but
recent research has identified the prokaryotic
cytoskeleton.

CYTOSKELETON
• Cells possess a cytoskeleton that provides
a structural framework for the cell,
facilitates intracellular transport, supports
cell junctions and transmits signals about
cell contact and adhesion, and permits
motility.

STRUCTURAL ELEMENTS
• The cytoskeleton of each cell contains structural
elements of 3 main types as well as many accessory
proteins responsible for linking these structures to
one another, to the plasma membrane and to the
membranes of intracellular organelles.
1) Microfilaments
2) Intermediate filaments
3) Microtubuleswww.indiandentalacademy.com

BASIC STRUCTURE OF CYTOSKELETON
• Protein subunits
• Cross-linking proteins
• Motor molecules

MICROFILAMENTS
• 6 to 8 nm in diameter
• It consists of actin filaments
• Actin exists in two states , the monomeric protein G-
actin and filamentous F-actin.

• Actin monomers polymerize to form filaments.
• Actin polymerization is stimulated once nucleation
occurs.

• Actin filaments have polarity.
• Each microfilament has fast growing or
plus end and slow growing or minus
end.
• The actin monomers all orient with their
cleft towards the same end of the
filament, called the minus end.

• Thus, rapid polymerization of actin monomers on
plus ends of microfilaments can produce protrusions
on cell surface called Psuedopods.
• These psuedopods are critical for the ability of the
cell to migrate in directional fashion.

• Microfilaments organized as stress fibres serve as
contractile elements .
• These structures may be responsible for producing
contractility to generate directional force during cell
motility.

• Microfilament based structure-contractile ring is
critical for separation of cell into its two progeny
during cytokinesis.

• One of the actin associated proteins is myosin which
has the ability to convert chemical energy into
movement.
• Myosin motors bind to actin filaments in presence of
ATP to produce the movement of actin filaments.

• Myosin motors involved in cytokinesis and cell
motility are two headed, some of which are involved
in movement of membrane bound vesicles along actin
tracks.
• Adherens junctions and focal contacts associated with
actin cytoskeleton are involved in adhesion between
cells or between cell to surface

• Focal contacts possess specific transmembrane receptors
of integrin family that link cell to extracellular matrix on
outside of cell and microfilaments on inside.

• Cross- linking proteins:
alpha-actinin, villin, fimbrin, filamin
• Cross-linking proteins organize actin
filaments into bundles or networks.
• Alpha-actinin, villin and fimbrin bind
actin filaments into parallel bundles.

• Filamins organize actin filaments
into loose networks that give
some areas of the cytosol a gel
like consistency.

CLINICAL CONSIDERATIONS:
• Mutations in actin binding proteins can lead to
defects in motility.
• And also impaired cytokinesis.
• Hypertrophied cardiomyopathy.

INTERMEDIATE FILAMENTS
• 8-10nm in diameter .
• These rope-like intermediate filaments are constructed of
tetramers of rod like proteins that are tightly bundled into
long helical arrays.
• They consists of filaments of proteins which self assemble
into larger filaments.

 Intermediate filament binding proteins, bind to
intermediate filament and they link them into 3-
dimensional network that facilitates the formation of
cytoskeleton.
 Intermediate Filaments differ from microfilaments
and microtubules in that they do not have polarity.

• They are more stable structures than other
cytoskeletal elements and they also do not have
molecular motors.
• These filaments of proteins also bind intracellular
structures to each other and to plasma membrane
proteins.

• Intermediate filaments are organized within cells so
that they link cell surfaces and nucleus.
• They stabilize the structural integrity of the cell as
they have the highest tensile strength.

• At cell surface, intermediate filaments attach to
specific junctions called desmosomes and
hemidesmosomes.
• These junctions attach cell to neighbouring cells or
extracellular matrix.

TYPES OF INTERMEDIATE FILAMENTS
1. Keratins
2. Desmin
3. Vimentin
4. Glial fibrillary acidic protein
5. Neurofilaments
6. Nuclear lamins

1) Keratins
• Type I – Acidic
Type II – Basic
• Found in epithelial cells and cells of hair and nails.
• These filaments form bundles, called tonofilaments,
that anchor on desmosomes.

2) DESMIN
• It is found in all types of muscle cells.
3) VIMENTIN
• Found in cells of embryo as well as cells of
mesenchymal origin : fibroblasts, leucocytes and
endothelial cells.

4) GLIAL FIBRILLARY ACIDIC PROTEIN
• GFAP is expressed in the central nervous system in
astrocyte cells.
• It is involved in many important CNS processes,
including cell communication and the functioning of
the blood brain barrier.

5) NEUROFILAMENTS
• Found in neurons.
• Forms the cytoskeleton of axons and dendrites.
6) NUCLEAR LAMINS
• Lining the nuclear envelopes of all cells.

CLINICAL CONSIDERATIONS
1) Skin diseases
• Mutations in keratin cause blistering diseases like
epidermolysis bullosa simplex(EBS) that results from
loss of cellular integrity.
• In this case, the keratinocytes of the epidermal basal
layer in the skin are rendered fragile by a mutation in
either K5 or K14, i.e., the pair of keratins that make
up the keratin cytoskeleton of these cells.www.indiandentalacademy.com

2) Squamous cell carcinoma
• K8 and K18 is the prototype keratin pair of simple
epithelia.
• K8 and K18 expression is not observed in stratified
adult epithelial tissues.
• However, they are often aberrantly expressed in
carcinomas including OSCC and their expression is
correlated with invasion and poor prognosis.

• A marked increase in the amount of tonofilaments in
the cytoplasm of tumor cells has been noted.
• It is proposed that tonofilament bundles provide
direct motive force for deformation of tumor cells,
which may eventually lead to the invasiveness of
these cells.

• The expression of vimentin is mainly regarded as
sign of a mesenchymal differentiation.
• Vimentin-positivity has repeatedly reported in
various carcinomas and was interpreted as sign of an
epithelial-mesenchymal transition, indicating an
increased metastatic potential .

Desmin-related myofibrillar myopathy
• It is the result of a mutation in the gene that codes for
desmin which prevents it from forming protein
filaments, instead forming aggregates of desmin.
• Alexander disease is a genetic disorder affecting the
central nervous system (midbrain and cerebellum). It
is caused by mutations in the gene for glial fibrillary
acidic protein (GFAP).

Mandibuloacral dysplasia
• It is a rare genetic disorder caused by mutations in
genes encoding nuclear lamins.

MICROTUBULES
• They are largest of all cytoskeletal
elements.
• 25nm in diameter.
• They are made up of two globular
protein subunits, alpha- and beta-
tubulin.

• The alpha and beta subunits form heterodimers which
aggregate to form long tubes made up of stacked rings.
• Each ring usually contain 13 subunits.

• Microtubules also have a fast growing or plus end
and a slow growing or minus end.
• Because of their constant assembly and disassembly,
microtubules are a dynamic portion of the cell
skeleton.

• Microtubules originate from specialized microtubule
organising centre: centriole.
• Microtubules in most cells are organized in a radial
array extending from a single site:centriole.

• Microtubules provide the tracks for transport of
vesicles, organelles such as secretory granules, and
mitochondria from one part of the cell to another.
• Also, microtubules function as cytoskeletal tracks for
mRNA transport .

• They also form the spindle, which moves the
chromosomes in mitosis.

• The functions of microtubules in vesicle transport and
chromosome segregation are dependent on molecular
motors that bind to and move along microtubule
tracks.

• These motor proteins are fascinating molecular machines
that convert chemical energy stored in ATP into
mechanical work and move along cytoskeletal tracks.
• Kinesin and dynein are two types of motors.

• Kinesin and dynein are two types of motors that
actively transport vesicles along the microtubules
(MTs) in cells towards the MT plus-end (cell
periphery) and minus-end (cell nucleus), respectively.

CLINICAL CONSIDERATIONS
1) Diseases associated with motor protein defects
• Kinesin deficiencies have been identified as cause
for Charcot-Marie-Tooth disease in which there is
defective axonal transport.
• Dynein deficiencies can lead to chronic infections of
the respiratory tract as cilia fails to function without
dynein.

2) The anticancer drug paclitaxel binds to
microtubules and makes them so stable that
organelles cannot move. Mitotic spindles cannot
form, and the cells die.
3) Tumor cells are often short of oxygen.
Carbonaro et al. explained how microtubules
(MTs) help to control production of a protein that
lets the cells survive.www.indiandentalacademy.com

• He showed that production of the transcription factor
Hif-1alpha , essential for a cell’s response to low
oxygen conditions is regulated by dynamic
microtubules.
• Hif-1alpha mRNA is transported along microtubules
and translated into protein – “ MICROTUBULES
HELP TUMOR CELLS BREATHE EASY”

• But disrupting the microtubule cytoskeleton with
drugs such as taxol or nocodazole shifts Hif-1alpha
mRNA into cytoplasmic structures called P-bodies,
where its translation is repressed by micro RNAs.
• This might be an additional way that microtubule-
targeting drugs kill tumor cells.

CYTOSKELETON BASED STRUCTURES
• Centrosomes
• Cilia
• Microvilli

CENTROSOMES
• Near the nucleus in the
cytoplasm of eukaryotic cells is a
centrosome.
• It is made up of two centrioles.
• Each with nine triplets of
microtubules arranged in a ring.
• During cell division the
centrioles replicate.www.indiandentalacademy.com

• The centrosomes are microtubule-organizing centres
that contain gamma-tubulin .
• When a cell divides, the centrosomes duplicate
themselves and the pairs move apart to form the poles
of the mitotic spindle, which is made up of
microtubules.

CILIA
• There are various types of projections from cells.
• True cilia are dynein-driven motile processes that are
used by unicellular organisms to propel themselves
through the water and by multicellular organisms to
propel mucus and other substances over the surface of
various epithelia.

• They resemble centrioles in having an array of nine
tubular structures in their walls, but they have in
addition a pair of microtubules in the centre and there
are two rather than three microtubules in each of the
nine circumferential structures.

MICROVILLI
• Microvilli are bundles of actin
filaments.
• Intestinal epithelial cells have
protrusions from their surface.
• These protrusions increase the
surface area of intestinal cells.

COMPARISON
PROTEINS MOTOR
MOLECULE
CROSS-LINKING
PROTEINS
MICROFILAMENT ACTIN MYOSIN ALPHA-ACTININ,
VILLIN, FIMBRIN,
FILAMIN
INTERMEDIATE
FILAMENT
KERATIN,
DESMIN,
VIMENTIN,
GFAP,
NEUROFILAMENT
------
FILAGGRIN,
PLECTIN
MICROTUBULE α-TUBULIN
Β-TUBULIN
KINESIN,
DYNEIN
MAP-1,
MAP-2,
MAP-4

CONCLUSION
• Microtubules and actin filaments are thought to form
the basic foundation of the cytoskeleton. The
microtubules are believed to be the overall organizers
of the cytoskeleton, affecting the position and
function of both actin filaments and intermediate
filaments. In addition, the movements of certain
organelles depend on microtubules.

Thus, cytoskeleton is a dynamic structure that:
• maintains cell shape
• often protects the cell
• enables cellular motion
• plays an important role in intracellular transport
• is very important in cell division.

THANK
YOU !!!

Cytoskeleton / fixed orthodontics courses

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