07-3-3cell Junction Surface

Cheng Xiaoli Zhengzhou University

Content
s
3.4. Overview
3.4.1 Tight junction
3.4.2 Anchoring Junctions
3.4.3 Gap Junctions
3.4.4 Cadherins
3.4
Overview
Because it is multicellular, the multicellular
organisms can use its environment in a complex
manner. Individual cell types are specialized to
perform different functions. However, certain
problems must be overcome for this division of
labor to work efficiently. Tissues must form in a
manner that enables component cells to
communicate with one another. Complex
mechanisms of cellular adhesion have evolved
allowing multicellular organisms to address this
task.
3.4
Overview
In animal cells there are three types of
junctions: tight junction , anchoring
junctions (including adherens junctions,
focal adhesion, desmosome,
hemidesmosome) and gap junction.
Cell-cell adhesion or cell-matrix
adhesion is mediated by transmembrane
proteins called cell adhesion molecules.
There are main groups: the cadherins ,
the integrins , the selectgins and the
immunoglobulin (Ig) superfamily. The
cadherins and the integrins often
3.4
Overview
•Junctional complexes are prevalent in
tissues that are subjected to extreme
stresses, such as epithelia, whereas
cell-matrix interactions are more
common in connective tissues.
• Cell-cell and cell-substratum adhesion
is important for:
•Tissue
integrity
•Morphogene
sis
•Cell
migration
•Cell growth
•Cell survival
3.4
Overview
Cell junctions are classified into three
function-ally distinct groups:
1. Tight junctions
2. Anchoring
junctions
= adhesion belt,
desmosome,
hemidesmosome
3. Gap junctions
Intestinal epithelium
Cheng Xiaoli cell
Zhengzhou University
3.4.1. Tight
Junctions
Tight junctions , also called Occluding
junctions , form a physical barrier that
prevents the leakage of even small
molecules between cells.

3.4.1. Tight
Junctions
Tight junctions are
located between
neighboring cells at the
most apical region of the
cells and appear as points
where the cell membranes
come into direct contact
with each other. Tight
junctions are composed of
anastomosing strands of
transmembrane proteins
that completely encircle
the cell.
• In many instances, the
indiscriminate diffusion
of molecules and ions
across the surface of an
epithelium would be
detrimental to main-
taining homeostasis.
• Tight junctions form a

physical barrier that
inhibits the leakage of
molecules from one side
of an epithelial sheet to
the other side.
3.4.1. Tight
Junctions
soluble molecules

3.4.1. Tight
Junctions

3.4.1. Tight
Junctions
Tight junctions ≠ fixedness
junction
• Tight junctions can regulate the
passage of molecules across these
natural barriers.
It restrict foodstuffs to the lumen and
allow amino acids, sugars, and other
molecules, to be directly routed to
the circulatory system.

3.4.1. Tight
Junctions
• Tight junctions, as part of the body's
normal activity, selectively open and
close in response to various signals both
inside and outside of cells, allow the
passage of large molecules or even
entire cells across the tight junction
• Tight junctions are found in all tissues,
barrier.
but those of particular relevance to drug
delivery include: nasal tissue,
gastrointestinal tissue ( where oral drugs
are absorbed), blood vessels and blood-
brain barrier. Cheng Xiaoli Zhengzhou University
3.4.1. Tight
Junctions
Molecular
Composition Tight junctions
consist of
Tight
Junctions glycoproteins, for
example, claudins,
occludins and
junctional adhesion
molecules that are
Adhesion
Junctions
anchored in the
membranes of two
adjacent cells and
interact with each
other to hold the
cells together and
3.4.1. Tight
Junctions
Molecular Tight junction
Composition membrane proteins
interact with scaffold
proteins (e.g., ZO-1) to
connect them with
various signal
transduc-tion and
transcriptional
pathways involved in
the regulation of tight
junc-tion function.

3.4.2 Anchoring
Junctions
Anchoring
junctions, provide
great strength and
are most numerous
in tissues that are
subjected to
extreme shear or
abrasive stress ,
such as the
epithelium of skin.
3.4.2 Anchoring
Junctions
• Classification
Anchoring junctions anchors cells
together allowing the tissue to be
stretched without tearing, and there
are four main types:
•Adherens junctions
•Desmosomes
junctions
•Hemidesmosomes
•Focal adhesions
3.4.2 Anchoring
Junctions
• Adhesions junction
Because zonule adherens form a continuous ring

around circumference of each cell, they are
sometimes called adhesion belts.
3.4.2 Anchoring
Junctions
• Adhesions junction
Cell-cell adherens
junctions, or zonula
adherens, are found
between the
neighboring cells in
epithelial sheets.
They are located in
the apical regions of
the cells, just below
the tight junctions.
3.4.2 Anchoring
Junctions
•
Desmosomes
•Desmosomes are sites
at the plasma
membrane between
adjacent cells where
mechanical and
chemical signaling
pathways
Desmosomesconverge.
tightly
link adjacent cells
but permit
materials to move
around them in the Cheng Xiaoli Zhengzhou University
3.4.2 Anchoring
Junctions
•
Desmosomes
•Desmosomes are sites
at the plasma
membrane between
adjacent cells where
mechanical and
chemical signaling
pathways
Desmosomesconverge.
tightly
link adjacent cells
but permit
materials to move
around them in the Cheng Xiaoli Zhengzhou University
3.4.2 Anchoring
Junctions
•
Desmosomes

3.4.2 Anchoring
Junctions
•
Desmosomes

3.4.2 Anchoring
Junctions
•
Desmosomes
In desmosomes,
the Ca+2
transmembrane
linker
glycoproteins
interact with Ca+2
linker proteins
that extend from
the surfaces of
hemidesmosomes
neighbo-ring cells,bind to components of
the extracellular matrix
whereas Cheng Xiaoli Zhengzhou University
3.4.2 Anchoring
Junctions
•
Desmosomes
Ca+2
Ca+2
The transmembrane glycoproteins of these

junctions are calcium-dependent adhesion
molecules known as cadherins.
3.4.2 Anchoring
Junctions
•
Desmosomes
•Anchored in dense plaques, cell adhesion

proteins cross the intercellular space, binding
adjacent cells together. Keratin fibers extend
through the cytoplasm from one plaque to University
Cheng Xiaoli Zhengzhou
3.4.2 Anchoring
Junctions
•
Desmosomes
•Anchored in dense plaques, cell adhesion

proteins cross the intercellular space, binding
adjacent cells together. Keratin fibers extend
through the cytoplasm from one plaque to University
Cheng Xiaoli Zhengzhou
3.4.2 Anchoring
Junctions
•
Desmosomes
•Desmosomes are
prominent adhesive
junctions in
epithelial cells.
•Around
desmosomal
cadherins known
as desmoglein and
Intermediate
filaments
desmocollin. Cheng Xiaoli Zhengzhou University

3.4.2 Anchoring
Junctions
•
Hemidesmosomes
Hemidesmosomes(HDs), as their name

indicates, appear as half-desmosomes,
under the electron microscope.
3.4.2 Anchoring
Junctions
•
Hemidesmosomes
Intermediate filaments of hemidesmosomes can

be observed terminating in electron-dense foci
of intra-cellular attachment proteins that dot the
internal surface of the plasma membrane, under
the electron microscope. Cheng Xiaoli Zhengzhou University
3.4.2 Anchoring
Junctions
•
Hemidesmosomes
• Unlike desmosomes , the binding
domains of hemidesmosomes
transmembrane of hemirane linker
glycoproteins do not attach to other
cells . instead, the linkers bind to
components of the specialized
extracellular
• Desmosomes matrix of the basal lamina.
and hemidesmosomes
are analogous, not homologous,
structures. Structural resemblance, but
no similarity at the molecular level.
3.4.2 Anchoring
Junctions
•
Hemidesmosomes
•Intermediate filaments are strong, elastic

polymers. Cheng Xiaoli Zhengzhou University
3.4.2 Anchoring
Junctions
•
Hemidesmosomes
Coupled to the
cytoplasmic surface
of the desmosome,
Intermediate
filaments form a
supracellular network
that strengthens
tissues, protecting
them against Cheng Xiaoli Zhengzhou University
3.4.2 Anchoring
Junctions
• Focal
adhesions
Focal adhesion or
focal contact, a
kind of adherens
junctions, is
important for both
cell-cell adhesion
and cellular
locomotion.
3.4.2 Anchoring
Junctions
• Focal
adhesions
•Cells attach to the
extracellular matrix
molecules through
integrin-type
membrane protein.
•Integrins are
hetero-dimers,
composed of an
Most alpha
integrin pairs are involvedand a beta
in linking the
subunit.
extra-cellular matrix to actin filaments at a
junction known as a focal contact.
Theα 6β 4 pair links the extracellular matrix to
intermediate filaments at junctionChengknown as aUniversity
Xiaoli Zhengzhou
3.4.3
Cadherins
• Cadherins are transmembrane
protein
• Adherens junctions and desmosome junctions
are both built around transmembrane
proteins belonging to the same
family, called cadherins: a
cadherin molecule in the
plasma membrane of one cell
binds directly to an identical
cadherin molecule in the
plasma membrane of its
neighbor.
3.4.3
Cadherins
Cadherins are
single-pass
transmembrane
proteins that
assume a stable
conformation in the
presence of
extracellular Ca +2
(calcium ions) .
When Ca +2 is
removed from the
extracellular
environment,
cadherins undergo a
3.4.3
Cadherins

3.4.3
Cadherins
Desmosomal Cadherins are transmembrane
Desmosomal Cadherins are transmembrane
glyco-proteins. There are two kinds of
desomosomal cadherins: Desmocollins
(Dsc1, Dsc2, Dsc3)
Desmogleins (Dsg1, Dsg2,
Dsg3 )
In the case of cadherins, binding requires also

that Ca 2+ (calcium) be present in the
extracellular medium. Cheng Xiaoli Zhengzhou University
3.4.3
Cadherins

3.4.4 Gap Junction
Gap junctions,
such as the
Communicating
junctions, attach
cells together in a
manner that allows
the transfer of
chemical or
electrical signals
between
3.4.4 Gap Junction

3.4.4 Gap Junction
• Gap junctions are formed by a grouping
of transmembrane proteins into a
structure called a connexon .
Intercellular
space
Protein
channels
connexon

3.4.4 Gap Junction
• Gap junctions are observed at regions
where plasma membranes of coupled
cells are closely juxtaposed .

3.4.4 Gap Junction
• However, unlike
tight junctions for
which the
membranes appear
the touch,
membranes
between adjacent
cells are separated
in region by slight
•gaps
Connexons of the
-- hence, neighboring cells adhere
to onegap
name another through extracellular
junction.
domains that align the proteins to form an
aqueous pore or channel through the
membranes of the two cells. Cheng Xiaoli Zhengzhou University
3.4.4 Gap Junction
• The result is that the
cytoplasm of one cell
is connected directly
to that of its neighbor
by aligned
hemichannels
contributed by each
cell. Small molecules
of relative molecular
mass below 1500Da
can readily move
between cellsisthrough
•The result that cells can be
gap junctional and electrically coupled.
metabolically
complexes.
Like other ion channels, gap junction
3.4.4 Gap Junction
A negatively stained electron

micrograph showing isolated gap
junctions.
3.4.5 Role of Cell junction and cell adhesion
Cell adhesion plays a crucial role in

embryogenesis, differentiation of adult
tissues and wound healing. The function
and regulation of intercellular junction
molecules in desmosomes and adherens
junctions act to mediate cell-cell adhesion
and attachment of the cytoskeleton to the
cell surface.
Norma Mutatio
l n
Dead skin cells
Epidermal cells
Basal cells
•Mutations can disrupt the assembly or

integrity of supracellular intermediate filament
networks lead to the weakening of the tissue.
•When subject to even mild mechanical stress,
the cells within the tissue can be damaged or
destroyed. Cheng Xiaoli Zhengzhou University
•Mutations can disrupt the assembly or

integrity of supracellular intermediate filament
networks lead to the weakening of the tissue.
•When subject to even mild mechanical stress,
the cells within the tissue can be damaged or
destroyed. Cheng Xiaoli Zhengzhou University
Pemphigu
Example s
1 ：importance
The
of desmosomes
in the
maintenance of
epithelial
integrity is
underscored in
human patients
with the
Pemphigu
Example
1：
s
These patients
produce
autoantibodies
that react
specifically with
the desmosomal
transmembrane
linker
glycoproteins .
This disrupts
desmosomes in
the skin, Cheng Xiaoli Zhengzhou University
Example Pemphigus
1 ： are two major of pemphigus.
There
• Pemphigus foliaceus.
• Pemphigus vulgaris.
In PF pathogenic autoantibodies are

directed against Dsg1. They impede its
function (by steric interference) and cause
a loss of adhesion between keratinocytes in
upper epidermis.
In PV pathogenic autoantibodies are
directed against Dsg3 causing and cause a
loss of adhesion between keratinocytes in
lower epidermis. Cheng Xiaoli Zhengzhou University
In PF the epidermis remains Pemphigu
largely intact so patients have s
a reasonable
prognosis PV is
almost always fatal if
untreated due to fluid
loss/infection.
It is not known what
causes the initial
sensitisation to self
antigens that results in
the production of
pathogenic antibodies.
Cell-cell adhesion is
essential for the
maintenance ofnormal Cheng Xiaoli Zhengzhou University
Pemphigu
s

Example Epidermolysis Bullosa,
2： EB
• A family of genetic (inherited)
blistering diseases of the skin that are
caused by defective cell-ECM (cell
extracellular
• EB is dividedmatrix ) adhesion.
into three main categories
based on where the loss of adhesion
occurs.
EB Junctional Dystrophic
simplex EB EB
• The 3 main types can be further sub-
divided into at least 27 clinical variants.
A pedigree of Epidermolysis
Bullosa
Proband

EB patients show a range of
phenotypes
EB simplex
(EBS): weber-
cockayne
subtype.
Generally
mild,
localised to
hands and feet

phenotypes
• Junctional EB:
Herlitz subtype.
• Poor prognosis
with significant
internal
involvement.
Mortality rate of
87% in first year.

phenotypes
Dystrophic EB: Hallpoeau-Siemens
subtype
At birth patients have large
areas of the body that are
completely devoid of skin
due to blistering.
Repeated blistering and
scarring throughout life can
lead to joint contractures and
pseudosyndactyly (fusion of
the fingers and tose).
Patients that survive
childhood are at
increased risk of
developing squamous
Mutations in keratins reduce the stress
resistance of cells. After physically stretching
cells that have mutations found in EBS
(epidermolysis bullosa simplex) patients, the
keratin filaments (green) start to break up and
Normal cells exhibit adhesion-dependent
growth; they must be attached (to other
cells or an extracellular matrix) for
survival. Cell adhesion transmits survival
signals, and loss of these signals triggers
apoptosis. Cells must not survive should
they migrate to a new tissue, where they
may exhibit unregulated growth. In fact,
most cancer cells have lost adhesion-
dependence. Growth in soft agar and
“piling”, characteristics of cells which
have lost adhesion-dependence, are also
A schematic summarizing the general
organization of the adherens junctions
Each different type of adherens junction is
composed of transmembrane linker glycoproteins
that interact with a cytoskeletal component
through an intracellular attachment protein.
Transmembrane
linker glycoprotein
Intracellular
attachment protein
Cytoskeletal
element
Plasma membrane
Transmembrane
linker glycoprotein
Extracellular mitrix
A schematic summarizing the general
organization of the adherens junctions
Appropriate component of each type of adherens
junction.
Junctional Type Cytoskeleta Transmembran Intracellul
complex l element e linker ar
glycoprotein attachment
Adhesion protein
Cell- microfilamen Cadherin Cadherin
belt/Zonul cell t s s
a
adherens
Focal Cell- microfilame Fibronectin Vinculin,
contacts matrix nt receptor Talin
/ and α-
adherens
plaques actinin
Desmoso Cell- Intermedia Desmocolli Plakoglobin
me/macul cell te filament ns and and
a Desmoglein desmoplaki
adherens s ns
Hemides Cell- Intermediat Laminin
mosome matrix e filament receptor
Overview
name function
tight junction seals neighboring cells together in
an epithelial sheet to prevent
leakage of molecules between
them
adherens joins an actin bundle in one cell to
junction a similar bundle in a neighboring
cell
desmosome “spot weld” that anchors the tough
junction intermediate filaments in one cell
to those in a neighbor
hemidesmosom anchors intermediate filaments in a
e junction cell to the basal lamina
gap junction cell-cell junction allowing
passage of small water-soluble
Cell Surface
Cell surface, surround in outside of cell, is
composite synthesis of structure and function.
It is a arena that connect with reaction
between cell and extracellular matrix, and
with verity complex functions.
Cell surface compose of lipid bilayers (as main

structure), cell coat and cytosol.

Transmembrane absorbed Transmembrane
proteoglycan glycoprotein glycoprotein
Cell coat
(glycocalyx)
membrane
Cell
Cytosol
Simplified diagram of a eucaryotic cell surface structure

Cell surface
Cell coat
Lipid
Bilayers
Cytosol

Functions of Cell
Surface
•To keep a stable inner circumstance,
•be distributed to
transport,
signal transmission,
cell recognition,
immunity reaction,
and other important action.
Segment
1
•The surfaces of most mammalian cells is

covered by a dense layer of complex
carbohydrates collectively known as the
glycocalyx(cell coat).

•Scientists saw earlier that in eucaryotic cells
many of the lipids in the outer layer of the
plasma membrane have sugars covalently
attached to them.
•The same is true for most of the proteins in the
plasma membrane. The great majority of these
proteins have short chains of sugars, called
oligosaccharides, linked to them, they are called
glycoproteins.
•Other membrane proteins have one or more
long polysaccharide chains attached to them;
they are called proteoglycans.
Cell Coat or
Glycocalyx
glycoproteins glycolipids proteoglycans
short chains of sugars The sugars The long chains of

(oligosaccharides) covalently sugars linked to
linked proteins attached to lipids proteins.

cytosol plasma
glycolipids nuclear membrane

All of the carbohydrate on the glycoproteins,
proteoglycans, and glycolipids is located on
one side of the membrane, the noncytosolic
side, where it forms a sugar coating called
the glycocalyx.

Intestinal lumen cell

Something more of
Cell Surface
Carbohydrates
•Nine different sorts sugars can be joined
together in different ways and in varied
sequences, often forming branched short or
oligosaccharides chains.
•Even three sugar groups can be put together
in different combinations of covalent linkages
to form hundreds of different tri-saccharides.

Something more of Cell
Surface Carbohydrates
In a multicellular organism the glycocalyx
can thus serve as a kind of distinctive
clothing that is characteristic of cells
specialized for a particular function and is
recognized by other cells with which they
must interact.

3-dimensional 2-dimensional
use fluorescent-tagged lectins or antibodies - detection of the

sialoglycoprotein CD43 (the main bearer of glycans on these
cells) on human Jurkat cells Cheng Xiaoli Zhengzhou University
In the past few years an expanded range of methods
have been developed for prying into the structure of the
glycocalyx and have resulted in the type of
representations shown below:

A closer
look
Cell surface oligosaccharides as well as the poly-
saccharides that are a key component of the extra-
cellular matrix are made up of monosaccharide
'building blocks'. These simple molecules, once
assembled into glycoconjugates form an incredibly
diverse array of structures

Biological functions of the glycocalyx
include:
1. Protection the cell surface from mechanical and
chemical damage
2. Protection from pathogens (or sensitivity to
pathogens)
3. Cell - cell communication
4. Interaction with, and binding of cell to, the
extracellular matrix
5. Modulation of immune responses
Segment 2Peculiarity structure
of cell surface
Usually, cell surface are uneven and lumpy.

With different cellular function and
physiological character there are many
special structures. Some of them stretch
out to the extracellular space, and some
protruding into the intercellular.

Segment 2Peculiarity structure
of cell surface
stretch out to the
extracellular space
Microvillus Folding Circular
Glycocalyx sharp
amoeboid
Small
phagocytosis Cell infolding
vesicle
protruding into
the intercellular
Microvi ll
us
Microvillus Functions: enlarge cell surface for
interaction, absorption, and hunt for antigens
or extrinsic body.

KEY
POINTS
• Please explain the following terms:
•tight junction
•desmosome
•hemidesmoso
me
•gap junction
•adherens
junction
•cell surface
•cell coat
• The functions of the cell
junctions ? Cheng Xiaoli Zhengzhou University

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Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

• Tight junctions form a

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

Because zonule adherens form a continuous ring

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

The transmembrane glycoproteins of these

•Anchored in dense plaques, cell adhesion

•Anchored in dense plaques, cell adhesion

desmocollin. Cheng Xiaoli Zhengzhou University

Hemidesmosomes(HDs), as their name

Intermediate filaments of hemidesmosomes can

•Intermediate filaments are strong, elastic

Cheng Xiaoli Zhengzhou University

In the case of cadherins, binding requires also

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

A negatively stained electron

Cell adhesion plays a crucial role in

•Mutations can disrupt the assembly or

•Mutations can disrupt the assembly or

In PF pathogenic autoantibodies are

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

Cell surface compose of lipid bilayers (as main

Cheng Xiaoli Zhengzhou University

Simplified diagram of a eucaryotic cell surface structure

Cheng Xiaoli Zhengzhou University

•The surfaces of most mammalian cells is

Cheng Xiaoli Zhengzhou University

glycoproteins glycolipids proteoglycans

short chains of sugars The sugars The long chains of

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

use fluorescent-tagged lectins or antibodies - detection of the

Cheng Xiaoli Zhengzhou University

Cheng Xiaoli Zhengzhou University

Usually, cell surface are uneven and lumpy.

Cheng Xiaoli Zhengzhou University

Microvillus Folding Circular

Cheng Xiaoli Zhengzhou University

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