cytoskeleton, junctions, fibroblast and ecm

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


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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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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cytoskeleton, junctions, fibroblast and ecm

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