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8/12/2019 Cytoskeleton, Junctions, Fibroblast and ECM
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Cytoskeleton
Cytoskeleton provides structural framework for the cell
Facilitates intracellular support
Support cell junctions and transmits signals about cell
contact, adhesion and motility
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Structural elements of
cytoskeleton:
Microfilaments
Intermediate filaments
microtubules
Microfilaments
Intermediate filaments
Cell-cellCell-matrix
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Microfilaments
6-8 nm in diameter
Consists of globular actin molecules polymerized into long
filaments
Form tracks for the movement of myosin and serves as
intracellular muscles concerned with the maintenance of
cell shape, movement and contractility
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Microfilament networks, along with actin-binding and actin
building proteins are found in association with adhesive
cell junctions, as a web beneath cell membranesActin interacts with other two components of cytoskeleton
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Intermediate filaments
Approximately 10 nm in diameter
Diverse protein composition
Not contractile but are important in the maintenance of
cell shape and contact between adjacent cells and
extracellular matrix
In cells of mesenchymal origin such as fibroblast and
osteoblast, intermediate filaments are the polymers of the
protein vimentin
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In epithelial cells, intermediate filaments consists of
cytokeratins
Intermediate filaments forms bundles called astonofilamentsthat anchor on desmosomes
Cytokeratins are a multigene family of proteins made up
basic and more acidic proteins
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Microtubules
Tubular and cylendrical structures with an average
diameter of 25 nm
Composed of protein tubulin arranged in rings stackedend to end, making up tubules
Microtubules provide internal support for the cell; are the
basis of motility for certain organelles, such as cilia
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Types of epithelia
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Intercellular Junctions
When cells come into contact with one another, and
sometimes with the extracellular matrix, specialized
junctions may form at specific sites on the contacting cell
membranes
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Class ification of cell Junctions
Occluding (tight) junctions : zona occludens
Adhessive junctionsa) Cell to cell
i. Zonula adherensii. Macula adherens (desmosomes)
a) Cell to matrixi. focal adhesions
ii. Hemidesmosomes
Communicating ( gap) junctions
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Classification of cell junctions
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A summary of the various cell junctions found in a vertebrate
epithelial cell, classified according to their primary functions
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On the molecular level,
intercellular junction typically
consists of three components:
A transmembrane adhesive protein
A cytoplasmic adapter protein and
A cytoskeletal filament
(These three com ponents d if fer
depending on the type of junct ion)
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Occluding ( tigh t) Junction
Opposing cell membranes are held in close contact by the
presence of transmembrane adhesive proteins arranged
in anastomosing strands that encircle the cell
The intercellular space is essentially obliterated at tight
junction
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The transmembrane
adhesive protein- occludin
andjunctional adhesion
molecule (JAM) interact
homotypically with same
proteins on the adjacent cell
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Adhesive Junction
Hold cells together or anchor cells to the extracellular
matrix
Intercellular space is maintained approximately 20 nm
Principal transmembrane proteins are members of
cadherinfamily
Cadherinsare calcium ion dependent proteins that
inetract homotypically with cadherinson the adjacent cell
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Zonula Adherens
The cadherin family member is E- cadherin, and
cateninare the cytoplasmic adapters, and actinfilaments
are the cytoskeletal component
The catenins and actin filaments are concentrated on the
cytoplasmic side of cell membrane at the zonula adherens
to form a dense web of actin at the apical end of the cells
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adherens
junctions
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Another transmembrane adhesive protein present in
zonula adherens is nectin, a member of the
immunoglobulin superfamily
Nectinhas important role during junction formation,
establishing the initial adhesion site and recruiting E-
cadherinand other proteins to the junctions
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Macula Adherens ( Desmosomes)
In desmosomes the cadherins
are desmogleinand
desmocollin
Interaction of these
transmembrane proteins with
those from the adjacent cellresults in a dense line in the
middle of the intercellular
space at the desmosome
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The catenins are desmoplakin, plakoglobin and
plakophilin,which form the electron dense plaque on the
cytoplasmic side of the desmosomes
This plaque serves as an attachment site for the
cytoskeletal components, which in case of desmosomes
are intermediate filaments
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Cell to matrix Junction
Similar to that of cell-cell adhesive junctions, but they use
different molecular components and attach the cell to the
extracellular matrix (ECM)
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Focal Adhesions
Transmembrane component is member of integrinfamily
of adhesion molecules
Binding of the integrinto collagen, laminin, fibronectin,and other ECM proteinsresults in recruitment and
remodelling of the actin cytoskeleton
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Hemidesmosomes
Link cell to the basal lamina and,
through additional extracellular
molecules, to the rest of ECM
Adhesive molecules present in
hemidesmosomes are integrin,
which binds specifically to basallamina glycoprotein laminin, and
collagen
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Gap Junctions
Plaque like regions of the cell
membrane where the intercelllar
space narrows to 2-3 nm
Transmembrane proteins of
connexinfamily form aqueous
channels between the cytoplasmof adjacent cells
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Epithelium- Connective Tissue Interface
All epithelia are separated from the underlying CT by a layer of
ECM organized as a thin sheet immediately adjacent to the
epithelial cells
This is c/a basal lamina- which is the product of the epithelium
and CT
Basal lamina, along with the hemidesmosomes,
attaches the epithelium to the underlying CT,
functions as filter to passage of molecules between epithelium and CT
Acts as barrier to cell migration
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Figure 19-4 Molecular Biology of the Cell( Garland Science 2008)
The transmembrane adhesion molecules link the
cytoskeleton to extracellular structures
interactions
Cadherins: cell-cell
Integrins: cell-matrix
Intergrins: bind laminin of the
basal lamina or fibronectinin
the ECM or to other cells
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Basal lamina thickness- about 50100 nm
2 structural components:
A) Lamina lucida: Adjacent to basal cell membrane
B) Lamina densa: between lamina lucida and CT
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Fibroblasts
Predominant cells of CT
Responsible for formation and maintenance of fibrous
components and the ground substance of CT
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Extracellular Matrix
It includes:
Collagen
Proteoglycans: glycosaminoglycans, hyaluronic acid
Glycoproteins: fibronectin, tenascin, thrombospondin
Growth factors and cytokines
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