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Cell-Cell Interaction

(Part 1: Cell
Junctions)
Varij Nayan1 and Anuradha
2
Scientist, CIRB,
Hisar-125001, Haryana, INDIA
Bhardwaj

1
2

Scientist, NRCE, Hisar-125001, Haryana, INDIA

INTERNE
T
WORLD

http://en.wikipedia.org/wik
i/File:Internet_map_1024.jp
g

Tree of Life !!!

Whole being greater than the


sum of individual parts

Of all the social interactions between


cells in a multicellular organism, the
most fundamental are those that hold
the cells together

Cell-Cell Interactions
Cell Signals one another with chemicals
(Cell Signalling)
Integration of cells into tissues : Cell surface
Proteins Mediates Cell-Cell Interactions
Expression of Cell Identity
Cell-Cell Adhesion- CAMs
Cell-matrix adhesion
CAMs and ECM can bind cell together, and
transfer of information between the exterior
and interior cells.

Different types have different Functions

cellular coat
Protection- water loss and wear
& tear
Cell junctions key to
Seal
Mechanical
stresses-transmitted by
surfaces
formation
and
cytoskeletal filaments
anchored to cell-matrix
Regulate
flow
of materials
& cell-cell
adhesion

maintenance of epithelial
sheets

Extracellular matrix directly bears mechanical


stresses

Molecular Biology of the Cell (2008, Garland Publishing) and Molecular Cell Biology (2004, W H Freeman)

Major Adhesive Interactions

Molecular Biology of the Cell (2008, Garland Publishing)

Major Adhesive Interactions

Molecular Cell Biology (2004, W H Freeman)

Major Adhesive Interactions

Molecular Biology of the Cell (2008, Garland Publishing)

. Adhesive Interactions

Molecular Cell Biology (2004, W H Freeman)

Transmembrane Adhesion Proteins

Molecular Biology of the Cell (2008, Garland Publishing)

Cell Adhesion Molecules


(CAMs)

Dont bind
each other

Ca2+
independe
nt

Molecular Cell Biology (2004, W H Freeman)

Cell Adhesion Molecules


(CAMs)

Cadherins- Classical Vs NonClassical


Name

Main Location

Classical (are major components of cell-cell adhesion)


E- Cadherin

Expressed on early embryonic cells


mammals. Later becomes restricted
embryonic and adult epithelial tissue

N- Cadherin

First mesodermal, later CNS (Neurons, heart,


skeletal m., kens and fibroblast)

P- Cadherin

Trophoblast cells (Placenta), epidermis, breast


epithelium

VE- Cadherin

Endothelial cells

in
to

Non-Classical Cadherins
Desmocollin Skin
Desmosoma
l
Lacks a
transmembran
e domain

Desmoglein
T-Cadherin

Skin
Neurons, muscle and Heart

Cadherin-23 Inner year, other epithelia


Fat
Epithelia and CNS
(Drosophila)

a Seven-Pass
Transmembra
ne Cadherin

Fat-1
(Mammals)

Epithelia and CNS

, and Protocadherins

Neurons

Flamingo

Sensory & some other epithelia

Cadherins and Cell-Cell


Adhesion
The C-terminal

cytoplasmic domain
associates with
cytoskeleton

The N-terminal
extracellular domains
form dimer and
through homoplilic
interactions, form
tetramers

Molecular Biology of the Cell (2008, Garland Publishing)

Cadherins and Cell-Cell


Adhesion

The cells segregate according to the cadherins they express

Molecular Biology of the Cell (2008, Garland Publishing)

Cadherins and Cell-Cell


Adhesion

Cadherin-dependent
cell sorting

Molecular Biology of the Cell (2008, Garland Publishing)

Compaction of an Early Mouse


Embryo

At eight-cell stage, begin to express E -cadherin

Molecular Biology of the Cell (2008, Garland Publishing)

Cadherins mediate Ca2+ -dependent homophilic


cell-cell adhesion

Extracellular domains of a classical cadherin (C-cadherin)


Molecular Biology of the Cell (2008, Garland Publishing)

Cadherins mediate Ca2+ -dependent homophilic


cell-cell adhesion

Ca binds in the hinge


regions
between
cadherin domains, and
prevent the flexing.
Without Ca the molecule
is floppy and adhesion
fails

Molecular Biology of the Cell (2008, Garland Publishing)

Hook and Loop Fasteners

Velcro !!!

Many
cadherin
molecules are in a
junction, functioning
like a Velcro.

Molecular Biology of the Cell (2008, Garland Publishing)

Epithelial-mesenchymal
transition
In mesenchymal cells the adhesion
molecules are switched of.
The transition is regulated by gene
regulatory
components
named
Slug, Snal and Twist. They afect Ecadherin expression
Twist suppresses E-cadherin. It is
involved
in
malignant
transformation.

Linkage of classical cadherin to actin


filaments

Molecular Biology of the Cell (2008, Garland Publishing)

Protein constituents of typical adherens


junction

Molecular Cell Biology (2004, W H Freeman)

Desmosome

Anchor
Proteins
Molecular Biology of the Cell (2008, Garland Publishing)

Molecular Biology of the Cell (2008, Garland Publishing)

Cell-cell junctions signalling

Level
of
p120-catenin
regulates cell junctions
Beta-catenin - wnt-signalling
Flamingo - as a GPCR
VE-cadherin - for response to
VEGF

Selectins
mediate cell-cell
adhesion in the
bloodstream
bind
carbohydrates
(lectins)

Molecular Biology of the Cell (2008, Garland Publishing)

Leucocyte- endothelial cells interactions

Molecular Biology of the Cell (2008, Garland Publishing)

Molecular Cell Biology (2004, W H Freeman)

Immunoglobulin superfamily
The
Ig-superfamily
members mediate Caindependent
cell
adhesion.
ICAM and VCAM (Cellular
Adhesion
Molecules)
bind integrins
Other types may have
homophilic binding

Molecular Biology of the Cell (2008, Garland Publishing)

Integrins: cluster into adhesive strs. In


nonepithelial cells

Molecular Biology of the Cell (2008, Garland Publishing)

Molecular Biology of the Cell (2008, Garland Publishing)

Molecular Cell Biology (2004, W H Freeman)

Molecular Cell Biology (2004, W H Freeman)

Fibronectin binding to Integrin

Molecular Cell Biology (2004, W H Freeman)

Tight Junctions

Molecular Cell Biology (2004, W H Freeman)

Gap Junctions

Molecular Biology of the Cell (2008, Garland Publishing)

Molecular Biology of the Cell (2008, Garland Publishing) and Molecular Cell Biology (2004, W H
Freeman)

Summary

Molecular Biology of the Cell (2008, Garland Publishing)

More Reading..
ECM of Epithelial Sheets- basal
lamina,
collagen,
laminin,
proteoglycans
ECM of Nonepithelial Tissuesfibrillar collagens, association
of
hyaluronan
and
proteoglycans, fibronectins
Plasmodesmata
Cell Signalling

Were the various types of cells to lose


their stickiness for one another and for
the supporting extracellular matrix, our
bodies would at once disintegrate and
flow of into the ground in a mixed
stream of cells.
Warren Lewis (1922)

Thank You

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