4. Cell Junctions

8/12/2019 4. Cell Junctions

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Cell-Cell Interaction


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Cells of a given type often aggregate

into a tissue to cooperatively perform a

common function

e.g. muscle contracts,xylem tissue in plants transports water.


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Different tissues can be organized

into an organ, again to perform one

or more specific functions.

e.g. The muscles, valves and blood vessels of a heartwork together to pump blood through the body.


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The assembly of distinct tissues

and their organization into organs

are determined by molecular

interactions at the cellular level bya wide array of adhesive molecules.


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1. Cell-Cell Adhesion

2. Cell-Matrix Adhesion

Type of Interactions


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Both types of cell-surfaceadhesion molecules are

usually integral membrane

proteins whose cytosolic

domains often bind tomultiple intracellular adapter

proteins. These adapters,

directly or indirectly, link theCAM to the cytoskeleton

(actin or intermediate

filaments) and tointracellular signaling

pathways.


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Types of CAM and receptor:

1. Cadherins

2. Immunoglobulin

3. Integrins4. Selectins


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Cell-adhesion molecules (CAMs) and adhesion receptors


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Cadherins are a family of at least 30

related glycoproteins that mediate Ca2+

dependent cell adhesion.

The classical cadherins contain a

relatively large extracellular segment

consisting of five tandem domains, a onetransmembrane domain and a one

cytoplasmic domain that binds p120

catenin and beta-catenin.

Beta-catenin can also bind to alpha-

catenin. Alpha-catenin participates in

regulation of actin containing cytoskeletalfilaments.

Cadherins


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Selectins

Selectins are a family of integral

membrane glycoproteins thatrecognize and bind to a particular

arrangement of sugars in the

oligosaccharides that project fromthe surfaces of other cells.

It possess a small cytoplasmicdomain, one transmembrane

domain and a large extracellular

domain.


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The name of this class of cell-surface molecule isderived from the word lectin a term for a

compound that binds to specific carbohydrate

groups.

There are three known selectins:

1. E-selectin (in endothelial cells)

2. L-selectin (in leukocytes)

3. P-selectin (in platelets and endothelial cells)

All three recognise sialylated carbohydrate groups.

Binding of selectins to their carbohydrates ligands

requires Ca2+

. Selectins, plays an important part ininflammation.


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Immunoglobulin are the integral

membrane proteins consist of

polypeptide chains composed of

number of Ig domains and a L1

molecule. Each Ig-type domains

composed of 70-110 amino acids

organized into a tightly foldedstructure.

Each L1 molecules contains a smallcytoplasmic domain, a

transmembrane segment and a five

Ig domain at the N-terminal portion.

Immunoglobulins

Ig domains

L1

L1

Ig domains


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Ig-type domains were present in wide variety of proteinswhich together forms the Immunoglobulin

superfamily or IgSF.

They are involved in various immune function but some ofthese proteins mediate calcium independent cell-cell

adhesion.

Most of the IgSF cell adhesion molecules mediate the

specific interactions of lymphocytes with cells required

for an immune response.

Some IgSF members such as VCAM (vascular cell

adhesion molecules), NCAM (neural cell adhesionmolecule) and L1 mediate adhesion between non-

immune cells


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CAMs mediate adhesive interactionsbetween cells of the same type

(homotypic adhesion) or between cells

of different types (heterotypicadhesion).

A molecules of one cell can directly bindto the same kind of molecules on an

adjacent cell (homophilic binding) or to

a different molecules (heterophilic

binding).


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In some cases, CAMs, adapters, andassociated proteins is assembled to form

a complex aggregate.

Specific localized aggregates of CAMs or

adhesion receptors form various types of

cell junctions that play important roles in

holding tissues together and facilitating

communication between cells and theirenvironment.


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1. Tight junctions (Cell-cell)

2. Adherens junctions (Cell-cell)

3. Desmosomes (Cell-cell)4. Hemi desmosomes (Cell-matrix)

5. Gap junctions (Cell-cell)

Types of cell junctions


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Tight junctions , lying just under the microvilli,

prevent the diffusion of many substances

through the extracellular spaces between thecells.

Adherens junctions, which connect the lateral

membranes of adjacent epithelial cells, are

usually located near the apical surface, just

below the tight junctions.

Epithelial and some other types of cells, such as

smooth muscle, are also bound tightly togetherby desmosomes, button like points of contact

sometimes called spot desmosomes.

Hemidesmosomes , found mainly on the basalsurface of epithelial cells, anchor an epithelium

to components of the underlying extracellular

matrix.

Gap junctions permit the rapid diffusion ofsmall, water-soluble molecules between the

cytoplasm of adjacent cells.


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Major roles of cell junctions:

1. Imparting strength and rigidity to a tissue.2. Transmitting information between the

extracellular and the intracellular space.

3. Controlling the passage of ions andmolecules across cell layers.

4. Serving passage for the movement of ions

and molecules from the cytoplasm of onecell to that of its immediate neighbour.


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I Occluding junctions

Tight junctions

II Anchoring junctions

Actin filament attachment sites

1. Adherens junctions (Cell-cell)

Intermediate filament attachment sites

1. Desmosomes (Cell-cell)

2. Hemi desmosomes (Cell-matrix)

III Communicating junctionsGap junctions

Classification of cell junctions


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Tight junctions

Tight junctions, lying justunder the microvilli, are the

closely associated areas of two

cells whose membranes jointogether to prevent the diffusion

of many substances through the

extracellular spaces betweenthe cells.


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It is a type of junctional complex only

present in vertebrates.

The corresponding junctions that occurin invertebrates are septate junctions.

Tight Junctions: Model


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Tight Junctions: Model

Tight junctions are composed

of a branching network of

sealing strands, each strand

acting independently from the

others. Therefore, the efficiency

of the junction in preventing ion

passage increases exponentiallywith the number of strands.

Each strand is formed from arow of transmembrane proteins

embedded in both plasma

membranes, with extracellular

domains joining one another

directly.


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Tight Junction Proteins

The two principal integral-membrane proteins found in tight

junctions are occludin and claudin. Both occludin and

claudin-1 contain four transmembrane helices, whereas thejunction adhesion molecule (JAM) has a single

transmembrane domain and a large extracellular region


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Tight junctions form seals

Tight junctions

prevent passage of

large molecules through

extracellular space

between epithelial cells.

This experiment,

demonstrates the

impermeability of tight

junctions in thepancreas to the large

water-soluble

lanthanum hydroxide.

T ll l & P ll l T t


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Transcellular & Paracellular Transport

In transcellular pathway, specific transport proteins in the apical

membrane import small molecules from the intestinal lumen into

cells; other transport proteins located in the basolateral membrane

then export these molecules into the extracellular space.

In epithelia with leaky tight

junctions, small molecules

can move from one side of

the cell layer to the other

through the paracellular

pathway


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Tight junction perform three vital functions:

1. They hold cells together.

2. They prevent the passage of molecules and ionsthrough the space between cells.

3. They block the movement of integral membrane

proteins between the apical and basolateral surfacesof the cell, allowing the specialized functions of each

surface to be preserved.



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Occluding junctions

Tight junctionsAnchoring junctions


1. Cell-cell (adherens junctions)


1. Cell-cell (desmosomes)

2. Cell-matrix (hemi desmosomes)

Communicating junctions

gap junctions


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Cell-cell adhesion

Adherens junctions Desmosomes

(Actin filament) (Intermediate filament)


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Adherens Junctions

Adherens Junctions


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Adherens Junctions

Adherens junctions,connect the lateral

membranes of adjacent

epithelial cells, are

usually located just

below the tight junctions.

Adherens Junctions


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Adherens Junctions

Adherens junctions occur

as a belt that encircleseach of the cells near its

apical surface. The cells

are held together bycadherin molecules

between the neighbouring

cells.

CAMs mediate cell-cell adhesion & link to


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cytoskeleton

The exoplasmic domains of

E-cadherin dimers clustered

at adherens junctions on

adjacent cells (1 and 2) formCa2+-dependent homophilic

interactions.

The cytosolic domains of theE-cadherins bind directly or

indirectly to multiple adapter

proteins that connect the

junctions to actin filaments(F-actin) of the cytoskeleton

and participate in intracellular

signaling pathways.


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In addition to their role in cell

adhesion, adherens junctions function

as communication centres that transmit

signals between neighbouring cells.


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Desmosomes

Desmosomes are

localized spot-like

adhesions randomly

arranged on the lateral

sides of plasma

membranes.

Desmosomes are

particularly numerous intissues that are

subjected to mechanical

stress, such as the skin.

Desmosomes: Model


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Desmosomes: Model

Cadherins of desmosomes

have a different domain

structure from that ofadherens junctions and are

referred to as desmogleins

and desmocollins.

Dense cytoplasmic plaques

on the inner surface of theplasma membranes serve as

sites of anchorage for looping

intermediate filaments.

Desmosomes


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Desmosomes

Desmosomes: Morphology


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Desmosomes: Morphology


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Occluding junctions

Tight junctionsAnchoring junctions


1. Cell-cell (adherens junctions)


1. Cell-cell (desmosomes)

2. Cell-matrix (hemi desmosomes)

Communicating junctions

gap junctions

Cell-Matrix Interactions: Model


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Integrin binds to Fibronectin


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g

Each fibronectin chain contains about 2446 amino acids and is

composed of three types of repeating amino acid sequences. Each chain

contains six domains, specific binding sites for heparan sulfate, fibrin,

collagen, and cell-surface integrins. The integrin-binding domain is alsoknown as the cell-binding domain.


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Hemidesmosomes


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Keratin Intermediate filament

Hemidesmosomes attach

one cell to the

extracellular matrix bycell adhesion proteins,

integrin.

In hemidesmosomes

the cell adhesion

molecules, integrin arelinked to intermediate

filaments on its cytosolic

domains.


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Anchoring filaments traverse the lamina lucida space and appearto insert into the electron dense zone, the lamina densa thereby

forming one of many potential adhesions between cell and matrix.


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Hemidesmosomes plays an important role in the

transduction of signals that are induced by the

extracellular matrix and which modulate processes asdiverse as cell proliferation, differentiation, apoptosis,

migration and tissue morphogenesis.

Thus it seems that hemidesmosomes do not merely

maintain dermo-epidermal adhesion and tissue integrity,

but that they are also implicated in intracellular signaling


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Gap junctions permit the rapid diffusion of

small, water-soluble molecules between

the cytoplasm of adjacent cells. Althoughpresent in epithelia, gap junctions are also

abundant in nonepithelial tissues and

structurally are very different from

anchoring junctions and tight junctions.

Gap junction link cells of nearly all

mammalian tissues.

Cell junctions: Gap Junctions


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Gap junctions have simple

molecular composition. They

entirely of integral membrane

protein called connexin.

Connexins are clustered within

plasmamembrane as a multiple

subunit, called Connexon thatcompletely san the membrane.

Gap Junctions: Morphology


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Summary: Cell junctions


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4. Cell Junctions

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